A Prospective Single Arm Trial Of Involved-field Radiotherapy For Stage I-II Low Grade Nongastric Marginal Zone Lymphoma
Funder
National Health and Medical Research Council
Funding Amount
$363,869.00
Summary
This is an international, multicentre study that will, for the first time, prospectively measure the curative potential of radiotherapy in localised marginal zone lymphoma (MZL). Most MZL arises in mucosa-associated lymphoid tissue (MALT), either in the stomach or in a range of other organs such as salivary glands, the tissues around the eye or the thyroid. Many stomach MALT lymphomas are caused by infection with Helicobacter Pylori. This infection can also be associated with non-gastric MALT ly ....This is an international, multicentre study that will, for the first time, prospectively measure the curative potential of radiotherapy in localised marginal zone lymphoma (MZL). Most MZL arises in mucosa-associated lymphoid tissue (MALT), either in the stomach or in a range of other organs such as salivary glands, the tissues around the eye or the thyroid. Many stomach MALT lymphomas are caused by infection with Helicobacter Pylori. This infection can also be associated with non-gastric MALT lymphomas, but the association has never been prospectively studied. Chlamydia Psittaci infection can cause MALT lymphoma in the orbit. The management of localised MZL outside the stomach is controversial and there have been no large prospective studies of any of the commonly-used treatments (radiotherapy, chemotherapy, surgery). No prospective studies have looked at the role of infection with Helicobacter pylori or the role of autoantibodies in these diseases. Radiotherapy is the best-characterised therapy in the literature and appears to have a high cure rate with low toxicity. The disease seems exquisitely radiosensitive. Management of localised MZL in Australia can be ad hoc and we have often seen patients who have undergone unnecessary mutilating surgery or ineffective chemotherapy. It has been reported that localised non-gastric MZL (stage I and II) can be cured with radiotherapy in a high percentage of patients (usually >70%) in retrospective studies from large centres such as Princess Margaret Hospital in Toronto. Workers from that centre will participate in this study. This study will: Prospectively report efficacy and toxicity for radiotherapy in MZL for the first time Definitively document Helicobacter Pylori status in all cases and Chlamydia status in orbital cases Provide a gold standard against which to compare new therapies This study won the award for the most highly supported study in its year at the TROG annual scientific meeting.Read moreRead less
Validation Of Stat3 As A Therapeutic Target In Diseases Arising From Its Inappropriate Activation By Gp130 Cytokines
Funder
National Health and Medical Research Council
Funding Amount
$674,142.00
Summary
Stomach cancer is the third most prevalent cancer in the Western World and result in the yearly death of several thousand people in Australia alone. We have discovered a specifice gene mutation of a receptor molecule called gp130 that results in the formation of stomach cancer in mice. We are now aiming to understand the exact molecular events by which this mutation results in the uncontrolled growth of stomach lining cells. We will employ a number of strategies to establish molecularly the exte ....Stomach cancer is the third most prevalent cancer in the Western World and result in the yearly death of several thousand people in Australia alone. We have discovered a specifice gene mutation of a receptor molecule called gp130 that results in the formation of stomach cancer in mice. We are now aiming to understand the exact molecular events by which this mutation results in the uncontrolled growth of stomach lining cells. We will employ a number of strategies to establish molecularly the extent to which this mouse model is informative for gastric cancer inhuman. In aprticular we will identify the genes that are involved in the progression of the disease. One important focus of the project is to see whether or not the moelcule (called Stat3) whose aberrant activation triggers the disease in the mouse could provide a future pharmacological target for intervention with the disease. Similarly with expertise of CIB, we will investigate with novel proteomics techniques whther we can identify a protein in the serum of these mice, which could give us aclue of whether or not the mouse ahs already developed disease. Such a protein could be of potentail diagnostic importance in the future to screen human for gastric cancer which in its eraly stages is usually without any clinical symptoms. In a related Aim we will find out the gene that can genetically cooperate with Stat3 and that is required to enable survival of newborn mice. It may well turn out mOur proposal combines the expertise of the two investigators in signal transduction and that this gene may be an important determinant to ensure that Stat3 triggers physiological rather than pathological responses in many differnet organs.Read moreRead less