Validation Of The Acceptability And Reliability Of Anal Swabs Used For Cytological Screening Among HIV+ MSM
Funder
National Health and Medical Research Council
Funding Amount
$76,108.00
Summary
This study will be screening HIV-positive men who have sex with men for Anal Squamous Intra-epithelial Lesions.These lesions, if left untreated, could develop into anal cancer. The study will take anal cytology swabs from 1000 HIV-positive men who attend the HIV clinic at St Vincent's hospital. Those men who are identified as having high-grade lesions (HSIL) or atypical cells (ASCUS) will be offered follow up by the principal investigator, Dr Richard Hillman.
HPV And Cervical Carcinoma: Signaling And Clinical Responses To Interferons
Funder
National Health and Medical Research Council
Funding Amount
$534,480.00
Summary
Cervical carcinoma and its treatment continues to be an important health concern in Australia. The interferons comprise an elaborate system of natural substances produced in the body, one of whose functions is to prevent cancer cells from developing. The interferons have been widely used to treat human diseases including viral infections and cancers caused by the wart virus. However, results of recent work indicates that viruses like the wart virus, HPV, have developed ways of inhibiting its eff ....Cervical carcinoma and its treatment continues to be an important health concern in Australia. The interferons comprise an elaborate system of natural substances produced in the body, one of whose functions is to prevent cancer cells from developing. The interferons have been widely used to treat human diseases including viral infections and cancers caused by the wart virus. However, results of recent work indicates that viruses like the wart virus, HPV, have developed ways of inhibiting its effectiveness. We have found that cervical carcinoma cells and virally infected cells resist the direct anti-cancer and anti-viral effects of interferons because they have abnormalities in their ability to respond to interferon. We have made good progress in understanding why these cells do not respond to the interferons. In particular they show a deficiency in the activity of cell proteins required to transmit the interferon signal inside the cells. The current proposal will allow us to gain a greater understanding of the processes inside cells that are taken over by the wart viral proteins and the reasons for its abnormality in interferon resistant cancer cells. We will determine whether the levels of certain genes in clinical samples from patients relates to their response to interferon treatment. This may allow us to establish a test to predict which patients will respond to interferon therapy, saving patients from ineffective treatment, side effects and cost. This study will have a broad significance to many human diseases where abnormalities in interferon signaling occur and will help to bring about the necessary changes in cell properties to overcome the abnormalities, restore the responses and improve the application of interferons to treat infectious diseases and perhaps other cancers as well.Read moreRead less
An Epidemic Of Vulvar Cancer In Young Women: Investigating The Role Of Human Papillomavirus And Genetic Susceptibility
Funder
National Health and Medical Research Council
Funding Amount
$489,706.00
Summary
Vulvar cancer is a rare disease; in 1993-1997 the age-adjusted incidence rate in Australia was 1.4 per 100,000 women (average 207 cases per year), similar to the incidence in most other countries. An epidemic of cases of vulvar cancer has been identified in younger Indigenous women living in remote communities in the Northern Territory (NT). Vulvar cancer is over fifty times more common in women aged less than 50 years in these communities than in the total Australian population. Women in these ....Vulvar cancer is a rare disease; in 1993-1997 the age-adjusted incidence rate in Australia was 1.4 per 100,000 women (average 207 cases per year), similar to the incidence in most other countries. An epidemic of cases of vulvar cancer has been identified in younger Indigenous women living in remote communities in the Northern Territory (NT). Vulvar cancer is over fifty times more common in women aged less than 50 years in these communities than in the total Australian population. Women in these communities also experience higher rates of high-grade Vulvar Intraepithelial Neoplasia (a pre-cursor to vulvar cancer), than elsewhere in the NT. Vulvar cancer is usually much more common in older women than younger women. In young women vulvar cancer and VIN are thought to be caused by infection with cancer causing strains of human papillomavirus (HPV), particularly the strain known as HPV16. In older women, vulvar cancer is not caused by HPV. In the remote communities in the NT, vulvar cancer is occurring almost entirely in young women, the amount of cancer occurring in older women in these communities is similar to the amount expected in the total Australian population. This project will investigate the cause of this epidemic of vulvar cancer and high-grade VIN. It will investigate whether HPV16 is more prevalent in these communities than elsewhere in Australia; whether there is a variant strain of HPV16 in these communites that is more virulent at causing cancer, and whether the disease occurs more commonly in families, which would mean that women in these communities inherit an increased susceptibility to vulvar cancer and VIN. This project will help to increase our understanding of vulvar cancer and VIN, help to control this epidemic, and inform whether the new HPV vaccines may be effective in preventing vulvar cancer in these communities.Read moreRead less
Non-viral Vectors For Targeted Delivery Of RNAi Nucleotides To Cervical Cancers
Funder
National Health and Medical Research Council
Funding Amount
$415,738.00
Summary
RNA interference (or gene silencing) is a new technique whereby we are able to turn off the expression of a particular gene either temporarily or permanently. Cancer is basically a genetic disease where certain protective genes are lost or cancer-causing genes expressed. Gene silencing holds great promise in the treatment of genetic disorders, infectious diseases and cancer. Cervical cancer is caused by infection with the human papillomavirus and the expression of two cancer-causing genes. Using ....RNA interference (or gene silencing) is a new technique whereby we are able to turn off the expression of a particular gene either temporarily or permanently. Cancer is basically a genetic disease where certain protective genes are lost or cancer-causing genes expressed. Gene silencing holds great promise in the treatment of genetic disorders, infectious diseases and cancer. Cervical cancer is caused by infection with the human papillomavirus and the expression of two cancer-causing genes. Using RNA interference we can turn off the expression of these two genes which results in the death of the cancer cell. We are also able to cure mice of tumours derived from human cervical cancer. The major issue with gene silencing is how to deliver it effectively to patients. Here we are investigating novel nanoparticulate systems to deliver this new gene-inhibiting drugs preferentially to the tumour site.Read moreRead less
Genetic And Environmental Factors In Invasive Cervical Cancer: A Twin Study.
Funder
National Health and Medical Research Council
Funding Amount
$769,637.00
Summary
Cervical cancer (neck of womb) is caused by human papillomavirus (HPV). Most women clear this very common virus. However persistent HPV infection can cause abnormal changes to cervical cells as found on Pap smears. Genetic factors may determine why such women ultimately develop cancer. A way to evaluate environmental from genetic effects is to study twins. If the risk is greater in indentical twins as compared to nonidentical it is more like to be due to genetics.
Regulation Of Nuclear Import Of Viral Oncoproteins And Transcription Factors By Protein-protein Interactions
Funder
National Health and Medical Research Council
Funding Amount
$650,383.00
Summary
The present application examines the controls that exerted over proteins that localize in the nucleus of eukaryotic cells. This relates relates integrally to cellular processes such as growth, development and oncogenesis. This research area is not represented elsewhere in Australia, and the particular experimental strategies to approach the problem, revolving around the use of special quantitative microscopic techniques are novel internationally. One part of the application seeks to examine tran ....The present application examines the controls that exerted over proteins that localize in the nucleus of eukaryotic cells. This relates relates integrally to cellular processes such as growth, development and oncogenesis. This research area is not represented elsewhere in Australia, and the particular experimental strategies to approach the problem, revolving around the use of special quantitative microscopic techniques are novel internationally. One part of the application seeks to examine transport within the cell of complexes of interacting proteins, rather than single proteins, under as close as possible to physiologically relevant conditions. This will be truly unique, and of great importance to our comprehension of eukaryotic cell function. This application examines particular types of negative control over protein nuclear localization. Since many proteins show such regulation, and in particular important proteins controlling cell growth and division, the results are fundamentally important to our understanding of how cells function in general. Further, this understanding may be applied in disease situations, such as viral-mediated oncogenesis. In the work we propose to do, viral proteins with functions relating to cancer will be examined in detail, as well as a cellular protein which is recognised by them - the tumor suppressor Rb. We intend to examine several viral oncoproteins which target Rb; one is a protein (E7) from the Human Papilloma Virus which has been frequently associated with cervical carcinomas and other cancers. Accordingly, the results may have direct application to viral-induced cancer, and our work may lead to understanding of the regulation of protein transport to the nucleus. This may thus afford a new approach at the pharmacological level to combat transformation.Read moreRead less