Investigation Of The Anticancer Action And Cytotoxic-synergism Of Matrix Metalloproteinase Inhibition.
Funder
National Health and Medical Research Council
Funding Amount
$272,036.00
Summary
In virtually all cases, death from solid tumors (including breast cancer) results from invasion and metastasis. The exciting recent pre-clinical observations that a new class of anticancer agents (which primarily target tumour invasion and metastasis) operate synergistically with a number of standard chemotherapy cytotoxics (such as those already used to treat breast cancer) suggests a new and significant additional therapeutic potential for both agents. The basis of this synergism is completely ....In virtually all cases, death from solid tumors (including breast cancer) results from invasion and metastasis. The exciting recent pre-clinical observations that a new class of anticancer agents (which primarily target tumour invasion and metastasis) operate synergistically with a number of standard chemotherapy cytotoxics (such as those already used to treat breast cancer) suggests a new and significant additional therapeutic potential for both agents. The basis of this synergism is completely unknown however, and it is our contention that this mechanism needs to be explored at the molecular level in order to identify which combinations will have most potential in the clinic. This proposal aims to characterize synergistic combinations in an animal model of breast cancer progression, and to determine the specific molecular mechanism of the process. Each phase of the proposed study is a worthwhile undertaking in itself, and while it makes primary use of a breast cancer growth and metastasis system, the information revealed should be relevant to many tumour types. This information can be used to formulate new therapeutic strategies for the treatment of solid tumours and their metastasis in patients.Read moreRead less
Analysis Of Very Early Cancer-related Methylation Abnomalities
Funder
National Health and Medical Research Council
Funding Amount
$422,310.00
Summary
The factors that are involved in triggering cancer are still unknown. Increasing evidence however indicates that the DNA in the pre-cancer cell becomes modified leading to altered expression of important genes called tumour suppressor genes. Often the DNA is deleted or mutated but it can also become chemically changed by a process called DNA methylation. We have found that an important tumour suppressor gene called p16 is inactivated and chemically methylated in breast epithelial cells at the st ....The factors that are involved in triggering cancer are still unknown. Increasing evidence however indicates that the DNA in the pre-cancer cell becomes modified leading to altered expression of important genes called tumour suppressor genes. Often the DNA is deleted or mutated but it can also become chemically changed by a process called DNA methylation. We have found that an important tumour suppressor gene called p16 is inactivated and chemically methylated in breast epithelial cells at the stage when the cell changes to a pre-cancer cell. This grant is aimed at finding what triggers the silencing and methylation of the p16 gene in this early pre-cancer stage. We also plan to identify other genes are methylated and undergo inactivation the pre-cancer breast cells. These results will have an impact on understanding the molecular mechanism that makes a breast cell susceptible to cancer and may lead to insights into new prevention and treatment strategies.Read moreRead less
A Comprehensive Analysis Of Myb Target Genes Involved In Myelopoiesis And Myeloid Transformation
Funder
National Health and Medical Research Council
Funding Amount
$511,294.00
Summary
The MYB gene is essential for both normal blood cell formation and the growth of leukaemia cells. It acts by switching other genes (target genes) on and off. This project aims to advance our understanding of how MYB functions, by carrying out a comprehensive search for MYB target genes. In particular it will focus on target genes that help explain MYB's ability to control cellular growth and maturation. Some of these target genes may provide leads for future anti-cancer drug development.
My work on human pigmentation genetics has provided a framework to understand normal variation in this physical trait and the associated genotypic risk factors for skin cancer development. The genes that determine an individual's skin phototype and the ce
Regulation Of Adult Colonic Crypt Homeostasis And Activation Of Colon Cancer Metastasis Genes By C-Myb
Funder
National Health and Medical Research Council
Funding Amount
$666,116.00
Summary
Regulation of normal colon biology and activation of genes involved colon cancer The c-myb gene is essential for the normal biology of the blood system and the colon. This gene is involved in regulating the balance between the production of new cells and their timely removal once they have completed their assigned tasks. There is a large body of evidence that supports the role of c-myb in the regulation of the blood system. We believe that the rules that govern the production of the huge number ....Regulation of normal colon biology and activation of genes involved colon cancer The c-myb gene is essential for the normal biology of the blood system and the colon. This gene is involved in regulating the balance between the production of new cells and their timely removal once they have completed their assigned tasks. There is a large body of evidence that supports the role of c-myb in the regulation of the blood system. We believe that the rules that govern the production of the huge number of cells needed to have a healthy blood system are similar if not identical to the rules used by the colon. This is because the colon also produces a massive number of cells each with special tasks and a defined life span of a few days. It is this rapid expansion of cell numbers and the programmed short life span of cells that necessitates multiple controls and very tight regulation. Furthermore if this process is hijacked by genetic changes that undermine these controls then there are numerous opportunities to initiate and potentiate malignant change or cancer. This project examines the role of the same genes in two contexts. Firstly when the genes are expressed at normal, highly regulated levels associated with the normal biology of the colon. The second context is when these genes are permitted to be over-expressed and thus drive processes for longer or in inappropriate situations leading to malignant growth.Read moreRead less
In this grant we aim to study the moecular basis of cancer. The promoter regions of tumour suppressor genes are often modified in cancer by a chemical process called methylation. Methylation of DNA is associated with gene silencing. Therefore DNA methylation is commonly regarded as causing the silencing of genes in cancer. In this grant, we aim to determine if methylation is causal in triggering gene silencing in cancer, or if methylation is a consequence of gene silencing. This is a critical di ....In this grant we aim to study the moecular basis of cancer. The promoter regions of tumour suppressor genes are often modified in cancer by a chemical process called methylation. Methylation of DNA is associated with gene silencing. Therefore DNA methylation is commonly regarded as causing the silencing of genes in cancer. In this grant, we aim to determine if methylation is causal in triggering gene silencing in cancer, or if methylation is a consequence of gene silencing. This is a critical distinction in understanding the role of methylation in cancer development.Read moreRead less
Regulation Of Expression Of The MicroRNA-200 Family
Funder
National Health and Medical Research Council
Funding Amount
$573,557.00
Summary
The majority of deaths from cancer are due to tumour metastasis. To metastasize, tumour cells must convert to a migratory form that can allow tumor cells to migrate and disseminate in the body. This process requires a genetic reprogramming of the cell. We have discovered that this genetic reprogramming is under the control of small RNA molecules called microRNAs. In this project we investigate what controls the levels of the microRNAs, to allow metastasis to occur in colon tumours.