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
The Human Papilloma Virus Oncoprotein E7 Degrades The Retinoblastoma Protein By Enhancing Calpain Activity
Funder
National Health and Medical Research Council
Funding Amount
$258,067.00
Summary
Cervical cancer is the second most prevalent cancer worldwide and the fifth leading cause of cancer deaths in women. Approximately 470,000 new cases are diagnosed annually. In most cases cervical cancer is thought to be caused by certain types of the human papillomavirus. Human papillomavirus makes a seies of proteins that cause the destruction of key host proteins in the cells they infect. This destruction is central to the formation of cervical cancer. We have recently discovered that we can p ....Cervical cancer is the second most prevalent cancer worldwide and the fifth leading cause of cancer deaths in women. Approximately 470,000 new cases are diagnosed annually. In most cases cervical cancer is thought to be caused by certain types of the human papillomavirus. Human papillomavirus makes a seies of proteins that cause the destruction of key host proteins in the cells they infect. This destruction is central to the formation of cervical cancer. We have recently discovered that we can prevent this destruction and rescue the key host proteins using inhibitors of the enzyme calpain. Here we seek to determine whether calpain inhibitors could find application in the treatment of human papillomavirus associated cancer.Read moreRead less
Identification Of Clinically Significant Subtypes Of Head And Neck Cancer Cells
Funder
National Health and Medical Research Council
Funding Amount
$469,122.00
Summary
Squamous cell carcinoma of the head and neck region (HNSCC) is amongst the top 10 most prevalent cancers. It is a life threatening cancer that is associated with a mortality rate of approximately 40%. Whilst most patients are treated with a combination of surgery, radiation and chemotherapy a significant fraction of patients relapse and eventually succumb to the cancer. The molecular basis for relapse in these patients is still unknown. One possible explanation for treatment failure is the notio ....Squamous cell carcinoma of the head and neck region (HNSCC) is amongst the top 10 most prevalent cancers. It is a life threatening cancer that is associated with a mortality rate of approximately 40%. Whilst most patients are treated with a combination of surgery, radiation and chemotherapy a significant fraction of patients relapse and eventually succumb to the cancer. The molecular basis for relapse in these patients is still unknown. One possible explanation for treatment failure is the notion that the cancer contains biologically distinct subtypes of cancer cells. Some these cells may respond to therapy whilst a small fraction of cells may not. If this small fraction of resistant cells were able to divide and repopulate the tissue then this would provide an explanation for relapse in these patients. However, as yet no such data has been available to support this argument. Most recently, studies with another cancer called acute myelocytic leukaemia has shown that they do contain a small subtype of cancer cells that are resistant to therapy and can regenerate the disease in patients. These cells have been called tumour initiating cells (TIC). In this application we will use patient tumour samples to try to isolate TICs from HNSCC. We will first determine whether these TICs exist and whether they express markers of normal human stem cells. We will also test whether these TICs are more resistant to chemotherapeutics or radiation than the rest of the tumour cells. In addition we will enrich for these TICs and identify new protein markers that could be used to test patient samples before or after treatment. This would be of considerable assistance in making decisions about treatment choice or prognosis. Since TICs have not been reported in HNSCC previously their identification would lead to a considerable advance in our undesratnding of how these tumours form.Read moreRead less
Role Of The Tetraspanin CD151 In Epithelial Biology And Cancer
Funder
National Health and Medical Research Council
Funding Amount
$454,500.00
Summary
A cell surface protein identified in this laboratory has been linked to cancer progression and metastasis. This project aims to examine the molecular basis of the action of the protein in regulating cell migration, and to establish model systems to provide definitive evidence as to its role in the development and progression of cancer. The models will also provide systems for future studies to evaluate the potential of antibodies and other inhibitors of the action of this protein as therapeutics ....A cell surface protein identified in this laboratory has been linked to cancer progression and metastasis. This project aims to examine the molecular basis of the action of the protein in regulating cell migration, and to establish model systems to provide definitive evidence as to its role in the development and progression of cancer. The models will also provide systems for future studies to evaluate the potential of antibodies and other inhibitors of the action of this protein as therapeutics in a range of human cancers.Read moreRead less
Characterisation Of The Role & Biomarker Potential Of The Novel Cell Surface Protein TTYH2 In Renal Cell Carcinoma
Funder
National Health and Medical Research Council
Funding Amount
$489,000.00
Summary
Renal cell carcinoma is the most common cancer of the kidney. One-third of patients upon first diagnosis have secondary tumour sites already within their body as well as new treatment approaches for more advanced disease making them very difficult to cure. An early specific test for this cancer is urgently needed. Our group has identified a new gene called TTYH2 which is highly expressed by renal cell carcinoma tissue samples but not in normal kidney tissues. In this study, we intend to look at ....Renal cell carcinoma is the most common cancer of the kidney. One-third of patients upon first diagnosis have secondary tumour sites already within their body as well as new treatment approaches for more advanced disease making them very difficult to cure. An early specific test for this cancer is urgently needed. Our group has identified a new gene called TTYH2 which is highly expressed by renal cell carcinoma tissue samples but not in normal kidney tissues. In this study, we intend to look at the expression of TTYH2 in more clinical samples to determine if TTYH2 will be a useful bio-marker for this cancer. We are also studying the function of this protein in renal cell carcinoma cells to identify the exact role that TTYH2 performs in cancer development and progression. Finally we will look at what other proteins are interacting with TTYH2 in kidney cancer cells. These latter studies will help us to understand the disease process better and may help us design new treatment methods.Read moreRead less
Value Of Androgen Deprivation And Bisphosphonate In Patients Treated By Radiotherapy For Localised Prostate Cancer
Funder
National Health and Medical Research Council
Funding Amount
$2,533,827.00
Summary
Following on from significant findings in the TROG 96.01 trial, the 03.04 trial, known as the RADAR trial was developed. This is a large-scale randomised controlled clinical trial currently conducted at 23 cancer treatment centres throughout Australia and New Zealand. The RADAR trial aims to recruit 1000 men with localised but inoperable prostate cancer. It was anticipated that the length of time required to enrol 1000 participants to the trial would be 5 years. However, because enrolment has ex ....Following on from significant findings in the TROG 96.01 trial, the 03.04 trial, known as the RADAR trial was developed. This is a large-scale randomised controlled clinical trial currently conducted at 23 cancer treatment centres throughout Australia and New Zealand. The RADAR trial aims to recruit 1000 men with localised but inoperable prostate cancer. It was anticipated that the length of time required to enrol 1000 participants to the trial would be 5 years. However, because enrolment has exceeded expectations and 728 patients have already been recruited, it is anticipated that the recruitment target will be reached in mid 2007. Patients are randomly assigned to receive one of four treatment options in the RADAR trial. The first option: Option A: Radiation Therapy and 6 months of Hormone Therapy (Leuprorelin acetate), is currently the standard of care. Option C is a further 12 months of hormone therapy after the current standard of care. Two of the options (B and D) are identical to options A and C except that subjects also receive 18 months of zoledronate (a 'bone' drug) in addition to hormone therapy and radiotherapy. The main goal of the RADAR trial is to determine whether 12 months of hormone therapy using Leuprorelin acetate starting immediately after standard therapy (ie 6 months of Leuprorelin acetate before and during radiotherapy) will reduce risk of return of the cancer, either within the prostate region or at remote sites in the body, and prolong life. An additional goal is to see whether 18 months of bisphosphonate therapy (bone density therapy) using zoledronate will reduce the risk of cancer returning in the bones as well as stopping dangerous bone thinning which can sometimes be caused by hormone therapy. The trial also seeks to determine whether the additional therapy given in this trial alters quality of life.Read moreRead less