ONTRANS: Oral Nicotinamide For Skin Cancer Chemoprevention After Transplant
Funder
National Health and Medical Research Council
Funding Amount
$624,824.00
Summary
The skin’s immune system is a key defence against skin cancer. Transplant recipients, who are chronically and profoundly immune suppressed to prevent rejection, have a 50-80 fold increase in skin cancer risk. Nicotinamide (vitamin B3) reduced skin cancer in our recent Phase 3 trial in immune competent individuals. A pilot study in renal transplant patients showed similar results. This project will determine at the Phase 3 level whether nicotinamide reduces skin cancers after kidney transplant.
Improving Outcomes Of Transplantation By Targeting Retrieval, Care And Complications
Funder
National Health and Medical Research Council
Funding Amount
$70,750.00
Summary
Our aim is to find out what the problems related to organ transplantation are in order to suggest ways of intervening to help reduce these problems for patients and the health care system. We will work closely with the team at one of Australia's leading transplant centres at Westmead Hospital to try and find safe and economic ways to tackle issues of organ shortage, those that come up during the organ donation and in the wider care of patients improve the practice.
Individualizing Cytomegalovirus Preventative Strategies Following Solid Organ Transplantation: A Precision Medicine Approach
Funder
National Health and Medical Research Council
Funding Amount
$128,224.00
Summary
Cytomegalovirus (CMV) infection is a significant contributor to poor outcomes following solid organ transplantation. Current preventative strategies are somewhat effective but treat groups of patients similarly rather than targeting the individual, so many patients are treated unnecessarily & breakthrough disease still occurs. We propose a program of research directed towards individualizing CMV prevention strategies in solid organ transplant recipients, incorporating new diagnostic tests.
Human Cytomegalovirus Encoded Control Of The Latent Phase Of Infection
Funder
National Health and Medical Research Council
Funding Amount
$639,871.00
Summary
Human cytomegalovirus has the ability to hide in the body of a person throughout their life time without it making them ill but the virus can awaken (reactivate) from this latent state and produce new virus. In immunosuppressed people such as transplant patients this reactivation causes significant problems, even death, yet this latency remains poorly understood. This project will help us to understand how the virus can hide successfully from the immune system in a latent form in the human host.
Combining Immune Monitoring And Immunotherapy To Tackle Cytomegalovirus Infections In Solid Organ Transplant Patients
Funder
National Health and Medical Research Council
Funding Amount
$801,416.00
Summary
Clinical management of infectious complications in kidney and heart/lung transplant patients remains significant challenge. Although prophylactic/pre-emptive treatment with antiviral drugs have shown dramatic improvements in the control of these infections, long-term treatment with these drugs is associated with significant toxicity, the appearance of drug-resistant virus isolates and significant health cost. In this proposal we will develop novel strategies to identify high risk patients and tr ....Clinical management of infectious complications in kidney and heart/lung transplant patients remains significant challenge. Although prophylactic/pre-emptive treatment with antiviral drugs have shown dramatic improvements in the control of these infections, long-term treatment with these drugs is associated with significant toxicity, the appearance of drug-resistant virus isolates and significant health cost. In this proposal we will develop novel strategies to identify high risk patients and treat these patients with killer T cells.Read moreRead less
Incidence And Risk Factors For Cancer After Liver And Cardiothoracic Transplantation
Funder
National Health and Medical Research Council
Funding Amount
$301,220.00
Summary
We will examine the incidence of cancer in patients before and after heart, lung, and liver transplantation. We will also examine the risk factors for cancer in these populations, including viral infection, time since transplantation, and the cause of organ failure. We will do this by linking data held by world-class Australian transplantation registries and the national cancer registry. Comparisons with other immune-deficient populations will allow valuable insight into the causes of cancer.
CONTINUING MECHANISTIC STUDIES OF UVA PHOTOIMMUNOPROTECTION
Funder
National Health and Medical Research Council
Funding Amount
$261,113.00
Summary
The UVB portion of sunlight causes sunburn, tanning, skin cancer, and suppresses immune function. Longer wavelength UVA is significantly less damaging, may contribute to photoageing and damage to deeper skin layers, but has been much less well studied. UVB-induced immunosuppression appears to be a prerequisite for skin cancer, and experimental protection from the immunosuppression results also in reduced severity of the long-term skin cancer outcome. We have identified a protective effect by UVA ....The UVB portion of sunlight causes sunburn, tanning, skin cancer, and suppresses immune function. Longer wavelength UVA is significantly less damaging, may contribute to photoageing and damage to deeper skin layers, but has been much less well studied. UVB-induced immunosuppression appears to be a prerequisite for skin cancer, and experimental protection from the immunosuppression results also in reduced severity of the long-term skin cancer outcome. We have identified a protective effect by UVA radiation against UVB-immunosuppression when UVA is administered to mice at non-burning environmentally relevant doses. This was an important and unprecedented finding, and is supported by recent observations also in humans. The aim of the present study is to clarify the mechanisms by which this resistance to UVB-induced immunosuppression is achieved, according to 2 main hypotheses: 1. UVA interferes with the actions of cis-urocanic acid, a natural epidermal UV-photoproduct that appears to initiate the immunosuppression by interacting with histamine. 2. UVA alters the balance of immunological control and thus activates normal antioxidant defences of the skin such as metallothionein and haem oxygenase, which antagonise the apparent oxidative requirement for UVB-immunosuppression. These pathways lead to the prediction that increasing the UVA component of the incident radiation will reduce skin cancer development. Humans typically receive disproportionately large UVA doses sunbathing through a UVB-sunscreen, or in cosmetic sunparlours. The assumption that UVA contributes to UVB skin damage may not be true at moderate UV doses, and a potential for UVA to protect from UVB-suppressed immunity and risk of skin cancer would suggest that broad spectrum sunscreens are contraindicated, and that the UVA effects need to be exploited.Read moreRead less
Patient Tailored Immunity Transplant For The Prevention Of Viral Infections Post Haemopoietic Stem Cell Transplantation
Funder
National Health and Medical Research Council
Funding Amount
$567,967.00
Summary
Blood or bone marrow transplantation can cure leukaemia and related blood disorders, but patients are susceptible to infections in the period early after transplant. Infectious complications remain a leading cause of death among allogeneic transplant recipients. Our research aims to prevent the onset of infection using novel cell therapies to rapidly restore the immune system thus preventing the problems associated with the transplant process.
Multiple Cytomegalovirus Infections: Biological And Evolutionary Significance.
Funder
National Health and Medical Research Council
Funding Amount
$555,776.00
Summary
This project involves the study of cytomegalovirus (CMV) a common viral infection of humans which normally cause little disease. However in individuals whose immune system is suppressed (such as AIDS patients or transplant recipients), or in infection of pregnant women, CMV can cause serious or life-threatening disease in the patient or foetus. An interesting feature of CMV diseases in such patients is that enhanced viral growth and more severe disease is frequently associated with the presence ....This project involves the study of cytomegalovirus (CMV) a common viral infection of humans which normally cause little disease. However in individuals whose immune system is suppressed (such as AIDS patients or transplant recipients), or in infection of pregnant women, CMV can cause serious or life-threatening disease in the patient or foetus. An interesting feature of CMV diseases in such patients is that enhanced viral growth and more severe disease is frequently associated with the presence of multiple strains of CMV in the patient. We suggest that mixed CMV infections provide a survival advantage to the virus, with different strains within the mixed infection assisting the growth of other strains. This would result in increased virus growth overall, and enhanced disease. To study the mechanisms by which multiple infections with different CMV strains may affect both the virus and the host, experiments will be performed using an animal model of CMV, murine cytomegalovirus (MCMV). We will examine the effect of the presence of multiple strains of virus on virus growth and distribution within the infected host. We will also determine if functional MCMV strains are capable of assisting non-functional strains to survive within the host. These studies are relevant to the design of a CMV vaccine, and will be valuable in revealing the ways in which viruses can co-operate within an infection.Read moreRead less
Cancer Incidence In Recipients Of Haematopoietic Stem Cell Transplantation In Australia
Funder
National Health and Medical Research Council
Funding Amount
$408,788.00
Summary
Haematopoietic stem cell transplantation (HSCT) is widely used in Australia to treat patients with haematological cancers. The risk of developing second malignancies after HSCT has been increasingly recognised over recent decades as more and more patients survive. The proposed study will characterise the incidence and risk factors for cancer following HSCT. This information is essential for long-term surveillance and intervention strategies in both specialist and primary care settings.