Matrix Metalloproteinases, Leukocytes And Menstruation
Funder
National Health and Medical Research Council
Funding Amount
$191,812.00
Summary
Menstrual bleeding problems are a common cause of pain and discomfort for women and often are satisfactorily treated only by hysterectomy. Despite this, little is known about the processes causing menstruation. Recently, we and others have demonstrated a role for a family of biological catalysts (enzymes) which break down the structure of the tissue lining the uterus (the endometrium) and are thought to cause menstrual bleeding. However, the mechanisms regulating their production during the norm ....Menstrual bleeding problems are a common cause of pain and discomfort for women and often are satisfactorily treated only by hysterectomy. Despite this, little is known about the processes causing menstruation. Recently, we and others have demonstrated a role for a family of biological catalysts (enzymes) which break down the structure of the tissue lining the uterus (the endometrium) and are thought to cause menstrual bleeding. However, the mechanisms regulating their production during the normal menstrual cycle is still largely unknown. Cells which come initially from the blood (leukocytes, particularly neutrophils and eosinophils) dramatically increase in numbers immediately prior to menstruation and these along with other cells, known as mast cells, start to produce a number of factors which we postulate are important for regulation of the enzymes. These cells, are also present in high numbers in endometrium of women with menstrual bleeding problems. This study will demonstrate that both the enzymes, and the leukocytes play a critical role in menstruation and will determine how the leukocytes in the endometrium are regulated. The studies have important implications for understanding and treating menstrual bleeding disorders.Read moreRead less
Chemoradiation And Adjuvant Chemotherapy Versus Radiation Alone In High Risk And Advanced Endometrial Cancer
Funder
National Health and Medical Research Council
Funding Amount
$460,832.00
Summary
This trial is evaluating whether adding chemotherapy during and after radiotherapy is better than giving radiotherapy alone in patients who have advanced or high risk endometrial cancer. One group of patients will be treated after surgery with both radiotherapy and chemotherapy, followed by additional cycles of chemotherapy and the other group will receive the standard treatment which is pelvic radiation alone. This study may result in a change in the management of these patients.
Early Events In Arteriolar Remodeling: Adaptation To Prolonged Vasoconstriction
Funder
National Health and Medical Research Council
Funding Amount
$415,750.00
Summary
Small arteries, while acutely responding to their environment with changes in diameter to regulate local blood flow and pressure, also undergo structural adaptation or remodelling. These events occur over a range of time-frames and involve both non-genetically and genetically regulated events. Thus a contractile event, while initially decreasing vessel diameter, also activates longer time frame processes which can span from rearrangment of cellular junctions-contacts to overt structural changes ....Small arteries, while acutely responding to their environment with changes in diameter to regulate local blood flow and pressure, also undergo structural adaptation or remodelling. These events occur over a range of time-frames and involve both non-genetically and genetically regulated events. Thus a contractile event, while initially decreasing vessel diameter, also activates longer time frame processes which can span from rearrangment of cellular junctions-contacts to overt structural changes within the vessel wall (for example thickening of the muscle layer). These adaptive processes may enable the forces of contraction to be maintained without continued energy expenditure and damage to the vessel per se. However, they can also contribute to long-term alterations in the control of blood pressure and perhaps contribute to states of hypertension as well as other common vascular diseases. For these studies we will use arterioles, isolated by microsurgical techniques, together with sophisticated computer and video-based approaches. These techniques allow arterioles to be studied under controlled conditions and relevant biochemical measurements performed. We will also use a cell model where cultured cells will be studied after defined periods of mechanical stimulation (for example stretch). Cells will be probed using a novel microscopic technique (atomic force microscopy) which enables the cell membrane to be studied with respect to changes in composition as well as physical characteristics (for example stiffness). The studies are relevant to our understanding of the normal adaptive processes occurring within blood vessels to control blood flow and pressure. The studies are also of direct relevance to our understanding of common vascular disease states including hypertension, complications of diabetes and chronic inflammatory disorders.Read moreRead less
Progenitor Origin And Regulation In Endometrial Regeneration
Funder
National Health and Medical Research Council
Funding Amount
$847,583.00
Summary
The endometrium is the lining of the uterus and regenerates each month during a woman's reproductive years. Stem and progenitor cells in the endometrium are thought to be responsible for this regeneration. We have identified a genetic marker for stem and progenitor cells in the endometrium of mice and will use this to understand endometrial regeneration. This work will address infertility as well as overactive endometrial growth in diseases such as endometriosis and endometrial cancer.
Endometrial cancer (uterine or womb cancer) is the most common invasive gynaecological cancer in Australia. Each year more than 1400 women are affected by the condition, and death is common amongst a subset with more aggressive disease. We plan to conduct a national study of endometrial cancer to identify options for prevention of the disease. No previous studies have looked at risk factors for endometrial cancer in Australian women. In particular, we hope to identify modifiable risk factors for ....Endometrial cancer (uterine or womb cancer) is the most common invasive gynaecological cancer in Australia. Each year more than 1400 women are affected by the condition, and death is common amongst a subset with more aggressive disease. We plan to conduct a national study of endometrial cancer to identify options for prevention of the disease. No previous studies have looked at risk factors for endometrial cancer in Australian women. In particular, we hope to identify modifiable risk factors for endometrial cancer, and identify genes that make some women particularly susceptible to the disease. There are at least two main types of endometrial cancer and limited evidence suggests that they may have different causes. Few studies have examined the two different types separately, and there is virtually no information regarding risk factors for the more aggressive forms. In addition, little is known about genetic factors that predispose women to endometrial cancer. In the present study, we will investigate which genes cause endometrial cancer in women who have a strong family history of the disease. We will also identify genes that are related to endometrial cancer in women with no obvious family history of cancer, and investigate how these genes interact with environmental factors (such as hormone replacement therapy and obesity) to cause disease. National epidemiological studies of other cancers are currently being conducted by our research groups within QIMR. In the present proposal, we will use our experience to build on the infrastructure and procedures already in place to conduct a new study on endometrial cancer. As one of the largest population-based studies of endometrial cancer ever conducted, it will be able to answer many of the questions that are currently unresolved. Moreover, answers will be relevant to Australian women and clinicians as well as to inform prevention strategies.Read moreRead less
Mechanistic And Translational Studies In Female Reproductive Health
Funder
National Health and Medical Research Council
Funding Amount
$631,370.00
Summary
The womb is essential for a health pregnancy. This research aims to determine how the womb interacts with embryos to ensure a healthy pregnancy forms. Cells in the womb can also grow abnormally and result in endometrial cancer. New treatments for endometrial cancer will also be tested in this research.
I am a cancer epidemiologist, specialising in molecular epidemiology. I investigate the genetic and environmental causes of gynaecological cancers, and their consequences (prognosis, survival, quality of life, economic).