A Randomised Trial Of Surgery Versus Surgery Plus Radiotherapy For Regional Control In Patients With Stage 3 Melanoma
Funder
National Health and Medical Research Council
Funding Amount
$305,163.00
Summary
Melanoma is a common disease in Australia. When it has spread to lymph glands it has a poor prognosis. If not controlled it can lead to severe local symptoms including pain, bleeding and disabilty. This is a world first clinical trial involving radiotherapy given after surgery for melanoma involving regional lymph glands. It involves a head to head comparison of surgery alone versus surgery followed by radiotherapy. The target is 230 patients, more than 160 being so far recruited. The main outco ....Melanoma is a common disease in Australia. When it has spread to lymph glands it has a poor prognosis. If not controlled it can lead to severe local symptoms including pain, bleeding and disabilty. This is a world first clinical trial involving radiotherapy given after surgery for melanoma involving regional lymph glands. It involves a head to head comparison of surgery alone versus surgery followed by radiotherapy. The target is 230 patients, more than 160 being so far recruited. The main outcome of the study is control of melanoma in the lymph gland basin. Other outcomes are survival, time to recurrence, side-effects (such as lymphoedema) and quality of life. The trial currently involves 13 centres in Australia, New Zealand and the Netherlands. It is expects to be completed in 2007.Read moreRead less
Characterisation Of Conserved Sox18-dependent Genes In Lymphatic Vascular Development
Funder
National Health and Medical Research Council
Funding Amount
$401,355.00
Summary
Lymphatic vessels are important in a number of diseases including lymphoedema and cancer. There is a significant gap in our basic understanding of how lymphatic vessels form. We have identified a series of genes that are regulated downstream of the lymphatic master gene Sox18 in mouse lymphatic vessels. This study aims to characterise these genes using complementary model systems. The genes and pathways identified will represent potential therapeutic targets in a number of disease contexts.
The Mechanism Of Ccbe1 Function During Lymphangiogenesis
Funder
National Health and Medical Research Council
Funding Amount
$502,437.00
Summary
Tumours induce the regional growth of lymphatic vessels (in a process termed lymphangiogenesis) and then spread (a process termed metastasis) via lymphatic vessels and lymph nodes. Inhibiting lymphangiogenesis can inhibit metastasis. We have identified a gene called ccbe1 that is essential for lymphangiogenesis during development. We aim to understand how this potential therapeutic target functions at the molecular level during lymphangiogenesis.
Defining The Molecular Events That Initiate The Genesis Of Lymphatic Vessels.
Funder
National Health and Medical Research Council
Funding Amount
$555,325.00
Summary
Lymphatic vessels are a vital component of the cardiovascular system. Abnormalities in the growth and development of lymphatic vessels are associated with human disorders including lymphoedema, cancer and inflammatory diseases. The focus of this application is to determine the molecular events that initiate the construction of lymphatic vessels, with the aim of identifying targets to which novel therapeutics for the treatment of lymphatic vascular diseases could be generated.
SNAC1:A Randomised Trial Of Sentinel Node Based Management Versus Axillary Clearance For Women With Small Breast Cancers
Funder
National Health and Medical Research Council
Funding Amount
$1,338,436.00
Summary
SNAC1 compares two operations for assessing cancer spread to the lymph nodes in women with early breast cancer: 1) axillary clearance and 2)sentinel node biopsy. Axillary clearance involves removal of most lymph nodes in the armpit. In sentinel node biopsy only a few lymph nodes most closely related to the breast cancer are removed. The trial will determine if sentinel node biopsy reduces lymphoedema and gives equivalent cure rates. If it does, then it should become standard practice.
SNAC1:A Randomised Trial Of Sentinel Node Based Management Versus Axillary Clearance For Women With Small Breast Cancers
Funder
National Health and Medical Research Council
Funding Amount
$240,187.00
Summary
Over 13,000 ANZ women are diagnosed with breast cancer each year. Most need surgery to remove the cancer and determine if it has spead to glands in the armpit (axillary lymph nodes). Knowing whether the cancer has spread to the axillary lymph nodes helps determine prognosis and plan treatment. Surgical removal is the most reliable way to assess the axillary lymph nodes. SNAC1 compares two operations for assessing cancer spread to the lymph nodes in women with early breast cancer: 1) axillary cle ....Over 13,000 ANZ women are diagnosed with breast cancer each year. Most need surgery to remove the cancer and determine if it has spead to glands in the armpit (axillary lymph nodes). Knowing whether the cancer has spread to the axillary lymph nodes helps determine prognosis and plan treatment. Surgical removal is the most reliable way to assess the axillary lymph nodes. SNAC1 compares two operations for assessing cancer spread to the lymph nodes in women with early breast cancer: 1) axillary clearance and 2) sentinel node biopsy. Axillary clearance involves removal of most lymph nodes in the armpit. In sentinel node biopsy only a few lymph nodes most closely related to the breast cancer are removed. Axillary clearance is the current standard operation. However, it is associated with risks including infection, pain, stiffness, numbness and lymphoedema (arm swelling). Lymphoedema may occur in 5-50% of women treated for breast cancer and can cause major suffering and disability. In many women their breast cancer has not spread to the lymph nodes, and axillary clearance is unnecessary. Recent studies suggest sentinel node biopsy may provide as much information as axillary clearance. Scans and dye are used to help locate the sentinel nodes. Minimising the amount of surgery to the armpit should reduce the side effects. However, the long term safety and effectiveness of removing only a few nodes is unknown. The trial will determine if sentinel node biopsy reduces lymohoedema and gives equivalent cure rates. If it does, then it should become standard practice. The study complements comparable studies being done in US, UK and Europe by providing unique information about arm symptoms and quality of life. SNAC1 recruited 1,088 women in 4 years. This application is for the work needed to report on outcomes after all women have been followed for 5 years.Read moreRead less
Molecular Mechanisms Of Lymphangiogenesis In Development And Disease.
Funder
National Health and Medical Research Council
Funding Amount
$303,828.00
Summary
Lymphatic vessels are a vital component of the cardiovascular system and serve several functions critical to embryonic development and adult health. These include: 1. The uptake, transport and return to the bloodstream of tissue fluid and protein. 2. The uptake and transport of lipids from the digestive tract. 3. The transport of cells of the immune system that fight infection. Abnormalities in the development and function of lymphatic vessels are associated with a large number of human diseases ....Lymphatic vessels are a vital component of the cardiovascular system and serve several functions critical to embryonic development and adult health. These include: 1. The uptake, transport and return to the bloodstream of tissue fluid and protein. 2. The uptake and transport of lipids from the digestive tract. 3. The transport of cells of the immune system that fight infection. Abnormalities in the development and function of lymphatic vessels are associated with a large number of human diseases. These include primary and secondary lymphoedema, inflammatory diseases such as psoriasis, rheumatoid arthritis and and asthma, and malignancies of the lymphatic vessels such as lymphangiosarcoma and Kaposi's sarcoma. Lymphatic vessels are also critical for the progression of many forms of cancer, by virtue of the fact that tumour cells exploit lymphatic vessels as a transport route for metastases. Diseases in which lymphatic vessels are involved therefore impact on a significant proportion of the Australian population. Our current knowledge of the mechanisms by which the lymphatic vascular network is constructed during embryonic development, and deregulated in disease states, is extremely limited. Once the molecular mechanisms of disease origin are established, much needed novel therapeutics to treat patients suffering from lymphatic vascular diseases can be designed. Treatments targeted to prevent the aberrant growth of lymphatic vessels are vital to halt tumour metastasis and the progress of inflammatory diseases, while treatments targeted to stimulate the development of new lymphatic vessels are necessary to treat diseases in which lymphatic vessels are hypoplastic, such as lymphoedema. This project aims to advance our understanding of lymphatic vascular development and function, in order to provide the opportunity to benefit patients suffering from all spectrums of lymphatic vascular disease.Read moreRead less
A Randomised Trial Of Interventions For The Management Of Lymphoedema After Axillary Treatment For Breast Cancer
Funder
National Health and Medical Research Council
Funding Amount
$151,250.00
Summary
As part of the management of early breast cancer, the axilla (armpit) is usually dissected surgically to determine whether the cancer has spread to the lymph nodes, and to lessen the chance of cancer recurring in this area. Information on lymph node involvement by cancer affects decisions about treatment, such as whether chemotherapy should be used. Surgical operations on the axilla can lead to nerve and muscle damage, and interfere with the flow of lymph (tissue fluid) from the arm, which resul ....As part of the management of early breast cancer, the axilla (armpit) is usually dissected surgically to determine whether the cancer has spread to the lymph nodes, and to lessen the chance of cancer recurring in this area. Information on lymph node involvement by cancer affects decisions about treatment, such as whether chemotherapy should be used. Surgical operations on the axilla can lead to nerve and muscle damage, and interfere with the flow of lymph (tissue fluid) from the arm, which results in swelling and discomfort (lymphoedema). Various treatments are available for lymphoedema, including massage, exercise and complession, but good information on their relative effectiveness in the short and long term are lacking. Evidence of effectiveness is important because some treatments involve considerable expense for patients and health care services, and the best treatment is the minimum treatment that is effective. Australian Consumers have called repeatedly for lymphoedema treatment trial research. A randomised controlled trial (RCT) is proposed with a follow-up period of four weeks for the reduction-phase treatment of lymphoedema. The trial will include a control group that receives no treatment except education on skin care. Women in the control group or with an insufficient response to sub-maximal treatment in the trial will receive a further four weeks of maximal treatment (not included in the trial). Only women who give informed consent will participate in the trial. The treatment combinations are (1) exercise; (2) massage; (3) compression; (4) exercise + massage; (5) exercise + compression; (6) massage + compression; (7) exercise + massage + compression. All women will receive skin care education. Women will be followed up with regular measurements of arm signs and symptoms.Read moreRead less
Sentinel Node Biopsy Versus Axillary Clearance In Early Breast Cancer: The SNAC Trial
Funder
National Health and Medical Research Council
Funding Amount
$1,257,525.00
Summary
Over 10,000 Australian women are diagnosed with breast cancer each year. Most need surgery to remove the cancer and determine if it has spread to glands in the armpit (axillary lymph nodes). Knowing whether the cancer has spread to the axillary lymph nodes helps determine prognosis and plan treatment. Surgical removal is the most reliable way to assess the axillary lymph nodes. This study compares two operations for assessing cancer spread to the lymph nodes in women with early breast cancer: 1) ....Over 10,000 Australian women are diagnosed with breast cancer each year. Most need surgery to remove the cancer and determine if it has spread to glands in the armpit (axillary lymph nodes). Knowing whether the cancer has spread to the axillary lymph nodes helps determine prognosis and plan treatment. Surgical removal is the most reliable way to assess the axillary lymph nodes. This study compares two operations for assessing cancer spread to the lymph nodes in women with early breast cancer: 1) axillary clearance and 2) sentinel node biopsy. Axillary clearance involves removal of most lymph nodes in the armpit. In sentinel node biopsy only a few lymph nodes most closely related to the breast cancer are removed. Axillary clearance is the current standard operation. However, it is associated with risks including infection, pain, stiffness, numbness and lymphoedema (arm swelling). Lymphoedema may occur in 5-50% of women treated for breast cancer and can cause major symptoms and disabilities. In many women the breast cancer has not spread to the lymph nodes, and axillary clearance is unnecessary. Recent studies suggest sentinel node biopsy may provide as much information as axillary clearance. Scans and dye are used to help locate the sentinel nodes. Minimising the amount of surgery to the armpit should reduce the side effects. However, the long term safety and effectiveness of removing only a few nodes is unknown. This trial will determine if sentinel node biopsy reduces lymphoedema and gives equivalent cure rates. If it does, then it should become standard practice. The study compliments comparable studies being done in US, UK and Europe by providing unique information about symptoms and quality of life from the women's perspective. One thousand Australian women will take part. The is study is being conducted by Australian breast surgeons under the auspices of the Royal Australasian College of Surgeons and the NHMRC Clinical Trials Centre.Read moreRead less
Rhythmicity, Synchronicity And Spasm In Smooth Muscle
Funder
National Health and Medical Research Council
Funding Amount
$614,520.00
Summary
Many cellular systems undergo rhythmical spontaneous chemical and-or electrical activity . This activity, often referred to as pacemaking, is prevalent in many organs underlying brain waves or causing heart beats or rhythmic contractions of smooth muscle. Our studies on pacemaker rhythmicities in smooth muscle have revealed a novel mechanism, one which is entirely different to that responsible for heart pacemaking, the generally held model for electrical pacemakers. We aim to study the mechanism ....Many cellular systems undergo rhythmical spontaneous chemical and-or electrical activity . This activity, often referred to as pacemaking, is prevalent in many organs underlying brain waves or causing heart beats or rhythmic contractions of smooth muscle. Our studies on pacemaker rhythmicities in smooth muscle have revealed a novel mechanism, one which is entirely different to that responsible for heart pacemaking, the generally held model for electrical pacemakers. We aim to study the mechanism in depth so that we can fully describe its operation. This knowledge will provide insight into phenomena such as spontaneous contractions in blood vessels, lymphatic vessels and in the gastrointestinal tract, activities which are the norm and which are likely to have major influence on blood pressure, the propulsion of lymph and gut peristalsis. The knowledge will in the longer term lead to a better understanding of rhythmicities generally as far ranging as uterine contractions during childbirth to brain waves. An understanding of the pacemaker mechanism may also provide a key to understanding debilitating conditions such as vasospasm which can lead to death or serious disability.Read moreRead less