Hormonal Influences In The Pathogenesis Of Ovarian Tumours
Funder
National Health and Medical Research Council
Funding Amount
$264,601.00
Summary
Ovarian cancer is one of the most common malignancies affecting the female reproductive system. We have found that two types of tumour of the ovary produce a hormone called inhibin; these tumours are also known to produce the steroid hormone estrogen. In these studies we are seeking to determine the genetic changes in the tumours that cause the production of these hormones. We suspect that these genetic changes are also the same changes which contribute to the development of the cancers. In orde ....Ovarian cancer is one of the most common malignancies affecting the female reproductive system. We have found that two types of tumour of the ovary produce a hormone called inhibin; these tumours are also known to produce the steroid hormone estrogen. In these studies we are seeking to determine the genetic changes in the tumours that cause the production of these hormones. We suspect that these genetic changes are also the same changes which contribute to the development of the cancers. In order to identify these genes we will draw on our knowledge of the genes that are important in the controlof growth and hormone secretion in normal ovarian cells. To assist this molecular analysis we will use two ovarian cell lines in culture that have many of the features of the primary tumours including inhibin secretion. We will also use new techniques to scan over 500 genes involved in tumours in general to see whether we detect any unusual or distinctive patterns in this sub-group of tumours. A genome wide scanning technique will be used to seek changes in the DNA of the tumours, inparticular loss of genetic material or amplification of regions. Identification of the genetic changes within these tumours should enable better systems of classification, enhance prognostication and provide specific targets for the development of appropriate treatment strategies.Read moreRead less
The Formation And Development Of The Ovarian Follicular Membrana Granulosa
Funder
National Health and Medical Research Council
Funding Amount
$351,575.00
Summary
In order for the ovary to be able to release eggs and produce hormones such as oestrogen, follicles must grow within the ovary. Each follicle contains one egg and when the follicle is large and filled with fluid it can rupture, releasing the fluid and egg in the process of ovulation. A key part of the structure of the follicle is a non-cellular layer called the basal lamina. This basal lamina encapsulates the inner cells, the egg and the fluid in the follicle. Each women has millions of follicle ....In order for the ovary to be able to release eggs and produce hormones such as oestrogen, follicles must grow within the ovary. Each follicle contains one egg and when the follicle is large and filled with fluid it can rupture, releasing the fluid and egg in the process of ovulation. A key part of the structure of the follicle is a non-cellular layer called the basal lamina. This basal lamina encapsulates the inner cells, the egg and the fluid in the follicle. Each women has millions of follicles prior to her birth, ten of thousands in her reproductive years, and none at the menopause. Since she only ovulates about 500 in her lifetime most follicles die in the process of growing to ovulatory size. This project will examine the structure of the follicle wall and the cells that make up that wall. How these cells replicate during follicle growth has never been discovered. This research has important implications for the many women who have polycystic ovarian disease, whose follicles fail to grow to full size. We will be examining these ovaries directly. The research also has importance in the next phase of IVF developments.Read moreRead less
Sellar Masses, Pituitary Adenomas And Pathways Of Pituitary Tumourigenesis
Funder
National Health and Medical Research Council
Funding Amount
$90,917.00
Summary
Pituitary tumours encompass a number of pathologies. Their cause is not clearly established. Pituitary adenomas are one of the most frequent intracranial tumours. The genetics of sporadic tumours is unknown. Craniopharyngiomas are rare brain tumours arising in the pituitary stalk area that can have profound effects, presenting in childhood or later. To date there is limited knowledge on the cell signaling pathways causing these tumors, which can help to understand cancer in general.
Studies Of The Dynamic Changes In The Ovarian Follicular Basal Lamina
Funder
National Health and Medical Research Council
Funding Amount
$305,557.00
Summary
In order for the ovary to be able to release eggs and produce hormones such as oestrogen, follicles must grow within the ovary. Each follicle contains one egg and when the follicle is large and filled with fluid it can rupture, releasing the fluid and egg in the process of ovulation. A key part of the structure of the follicle is a non-cellular layer called the basal lamina. This basal lamina encapsulates the inner cells, the egg and the fluid in the follicle. Each women has millions of follicle ....In order for the ovary to be able to release eggs and produce hormones such as oestrogen, follicles must grow within the ovary. Each follicle contains one egg and when the follicle is large and filled with fluid it can rupture, releasing the fluid and egg in the process of ovulation. A key part of the structure of the follicle is a non-cellular layer called the basal lamina. This basal lamina encapsulates the inner cells, the egg and the fluid in the follicle. Each women has millions of follicles prior to her birth, ten of thousands in her reproductive years, and none at the menopause. Since she only ovulates about 500 in her lifetime most follicles die during the process of growing to ovulatory size. This project will examine the follicular basal lamina in order to determine its role during follicle growth and development, and when follicles die. This has important implications for the many women who have polycystic ovarian disease, whose follicles fail to grow to full size. We will be examining these ovaries directly. The research also has importance in the next phase of IVF developments.Read moreRead less
This is a study of the biological system of epigenetics. Every cell in our body has the same genetics, or library of information contained in the form of DNA sequence. Epigenetics is the system that controls how this DNA is used in a particular situation, or what books are opened and read. During embryonic development, cells know what they want to become, e.g., a muscle cell, and, once they take on an identity, remember that they are when they duplicate themselves during growth. Epigenetics does ....This is a study of the biological system of epigenetics. Every cell in our body has the same genetics, or library of information contained in the form of DNA sequence. Epigenetics is the system that controls how this DNA is used in a particular situation, or what books are opened and read. During embryonic development, cells know what they want to become, e.g., a muscle cell, and, once they take on an identity, remember that they are when they duplicate themselves during growth. Epigenetics does not achieve this through changing genetics the library always stays intact. Rather, it acts by using proteins or chemicals to make DNA functional in one way, or another. Genomic imprinting is a special type of epigenetics. While an embryo has received identical genetic information from each of its parents, the epigenetic information received from each parent was not entirely the same. Some genes which behave differently according to what parent they came from. For example, a gene that makes a growth factor protein is active only if received from the father. If received from the mother, it is inactive, and makes no protein. Genes behaving in this way are known as imprinted genes. We are trying to discover what epigenetic mechanisms are behind this behaviour of imprinted genes. One way we are approaching this problem is to study germ cells the cells giving rise to eggs and sperm. These cells are unusual in that their imprinted genes behave in the same way regardless of whether they were received from the mother or father, i.e., like any other gene. If we can understand why this is the case, we will be better able to understand why imprinted genes behave the way they do in the rest of the cells of the body. Broadly, the mechanisms we uncover should further our understanding of germ cell development, gene expression, and disease. Perturbations in the epigenetic profile are likely causes of human disease, including cancer.Read moreRead less
Nfib Regulates Glial Differentiation During Development And Disease Via Repression Of The Key Epigenetic Protein, Ezh2
Funder
National Health and Medical Research Council
Funding Amount
$572,912.00
Summary
Glial development is critical during development, and unrestrained proliferation of glial stem cells in the adult can lead to deadly brain cancers such as glioma. At present there is no cure for glioma and current treatments do not significantly delay tumour progression. Nfib is a transcription factor that may prevent tumour growth through cellular differentiation. We will investigate the role of Nfib during development and in the pathogenesis of glioma and its potential as a therapeutic target.
The Role Of TAP And MHC Class I Expression In The Response To Melanoma Immunotherapy Using Autolgous Dendritic Cells
Funder
National Health and Medical Research Council
Funding Amount
$337,811.00
Summary
Treatment for patients with malignant melanoma whose disease has spread, or metastasised, to sites distant from the original melanoma is usually unsuccessful. At this stage of the disease there is no known curative treatment with conventional surgery, radiation or chemotherapy. Occasionally, however, melanoma in its early stages is successfully dealt with by the natural response of the immune system. In these cases, the immune system generates cancer-controlling killer T lymphocytes that enter t ....Treatment for patients with malignant melanoma whose disease has spread, or metastasised, to sites distant from the original melanoma is usually unsuccessful. At this stage of the disease there is no known curative treatment with conventional surgery, radiation or chemotherapy. Occasionally, however, melanoma in its early stages is successfully dealt with by the natural response of the immune system. In these cases, the immune system generates cancer-controlling killer T lymphocytes that enter the melanoma and kill the tumour cells. Killer T lymphocytes are generated by the lymph glands when the immune system is presented with melanoma cell components, or antigens, by specialised cells known as dendritic cells. This project consists of a clinical trial that aims to boost the natural ability of the immune system to generate killer cells by growing dendritic cells from the blood, mixing them with melanoma antigens, and then inject the mixture. When injected into the skin, dendritic cells quickly move to lymph glands to generate killer T lymphocytes. T lymphocytes can find their way to melanoma deposits all over the body. The reasons for response or non-response to the vaccination will particularly be assessed in this project.Read moreRead less