Airway Inflammation In Asthma And Chronic Obstructive Pulmonary Disease
Funder
National Health and Medical Research Council
Funding Amount
$390,509.00
Summary
In chronic diseases of the airway such as asthma and airway narrowing due to cigarette smoking - chronic obstructive pulmonary disease (COPD), the airways show inflammation (increased numbers of cells and their products) and remodelling (increased thickness and scarring) which persist for many years, possibly indefinitely. The exact mechanisms by which inflammation persists in the airway wall in asthma and COPD are unknown. We and others have shown that greater numbers of memory T-lymphocytes (T ....In chronic diseases of the airway such as asthma and airway narrowing due to cigarette smoking - chronic obstructive pulmonary disease (COPD), the airways show inflammation (increased numbers of cells and their products) and remodelling (increased thickness and scarring) which persist for many years, possibly indefinitely. The exact mechanisms by which inflammation persists in the airway wall in asthma and COPD are unknown. We and others have shown that greater numbers of memory T-lymphocytes (T-cells) are present in the airway wall in asthma and COPD. T-cells orchestrate the processes involved in inflammation. We have hypothesised that the persistence of airway inflammation in asthma and COPD results from the proliferation of memory T-cells within the airway wall. Unlike na ve T-cells, memory T-cells have previously been stimulated and can easily be activated to proliferate and promote inflammation by other cells which are fixed in the airway. Data from our current work examining this process suggests that, although cells fixed in the airway such as fibroblasts and macrophages are activated in asthma and COPD and may activate T-cells, they do not seem to be causing T-cell proliferation. We now wish to extend these studies by determinimg if memory T- lymphocytes are proliferating in the airway wall within aggregations of lymphoid cells which act like lymph nodes and promote T-cell growth. To do this we will compare the number of these aggregations and the types of T-cells they contain in mild and severe cases of asthma and COPD with those in normal subjects. This work will provide new knowledge to help understand the mechanisms for the persistance of airway inflammation in asthma and COPD and may thereby also provide a focus for effective treatments of these condition.Read moreRead less
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
Roles Of Integrin Receptors And The Helicobacter Pylori Protein CagL In Gastritis And Gastric Cancer
Funder
National Health and Medical Research Council
Funding Amount
$290,697.00
Summary
How the bacterium Helicobacter pylori (Hp) causes gastritis and gastric cancer in the stomach is not well understood. Here we investigate the molecular languages used by Hp to deregulate the normal functions of the human stomach cells. The research outcomes will on one hand help us to better understand how Hp causes diseases, and on the other hand, facilitate the development of new antibiotics or treatment therapies to combat gastric cancers and gastritis.