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.
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
Role Of Endogenous Opioid Peptides In Endometrial Receptivity And Placentation
Funder
National Health and Medical Research Council
Funding Amount
$523,884.00
Summary
Infertility affects 1 in 10 couples. In early pregancy miscarriage is the commonest complication resulting in the loss of 10-15% of all conceptions. During the latter part of pregnancy, complications such fetal growth restriction and preeclampsia, affects up to 10% of women resulting in considerable suffering to the mother and her newborn. Many of these births are premature with neonates requiring intensive care. There is also good evidence that children who are born prematurely with low birth w ....Infertility affects 1 in 10 couples. In early pregancy miscarriage is the commonest complication resulting in the loss of 10-15% of all conceptions. During the latter part of pregnancy, complications such fetal growth restriction and preeclampsia, affects up to 10% of women resulting in considerable suffering to the mother and her newborn. Many of these births are premature with neonates requiring intensive care. There is also good evidence that children who are born prematurely with low birth weight are much more likely to develop a host of diseases including cardiovascular disease, diabetes and obestiy in adult life increasing the long term burden of health care support. Infertility is often due to the lack of uterine endometrial receptivity while the pregnancy complications arise from the reduced growth of the placenta and sub-optimal interactions between the mother's uterus and the growing placenta. Endometrial infertility, placental growth and interactions with the endometrium is stringently regulated by substances produced at the maternal endometrial- placental interface. To understand how infertility and pregnancy complications arise, develop diagnostic, monitoring and therapeutic tests it is critical to understand the roles played by these regulatory substances. We have novel data suggesting that small proteins known as endogenous opioids could be enchancing endometrial receptivity and the growth and development of the placenta. Interstingly these substances are closely related to exogenous opioids such as heroin and morphine. We will investigate the manner in which these substances regulate endometrial immune cell function, maintain the endometrial stromal cell bed in preparation for pregnancy and direct the growth and differentiation of the placenta. The findings will give novel insights into infertility, improve the success rates of in vitro fertilization, reduce maternal and neonatal complications of pregnancy.Read moreRead less
Proprotein Convertase 6: A Master Regulator For The Development Of Endometrial Receptivity And Embryo Implantation
Funder
National Health and Medical Research Council
Funding Amount
$424,846.00
Summary
Implantation of an embryo into the womb (uterus) is a key step for human development, without which the embryo will only be able to develop to a very early stage the blastocyst stage (about 8 days after fertilization). For successful implantation, the uterus has to prepare itself to be receptive; this preparation is crucial as an ill-prepared uterus will reject the embryo. Such implantation failure is a major cause of early pregnancy loss and female infertility; ~30% of pregnancies end in sponta ....Implantation of an embryo into the womb (uterus) is a key step for human development, without which the embryo will only be able to develop to a very early stage the blastocyst stage (about 8 days after fertilization). For successful implantation, the uterus has to prepare itself to be receptive; this preparation is crucial as an ill-prepared uterus will reject the embryo. Such implantation failure is a major cause of early pregnancy loss and female infertility; ~30% of pregnancies end in spontaneous abortion. How the uterus becomes receptive is not well understood. Our recent research has identified that proprotein convertase 6 (PC6), an important master switch responsible for activating other proteins, is tightly regulated in the uterus during its preparation for receptivity and critical for implantation. This project will examine how PC6 acts in the human uterus to make it receptive, by identifying the factors that PC6 controls and how this controlling works. We will use a cell culture model with cells isolated from human term placenta. In addition, there is no means of readily testing whether the uterus is receptive owing to the lack of reliable biomarkers. In this study we will determine whether PC6 (and those molecules controlled by PC6) are potential biomarkers for uterine receptivity. This will be achieved by examining uterine biopsies and uterine washings collected from proven fertile volunteers and patients of proven endometrial infertility. This study will greatly enhance our understanding of how a critical molecule, PC6, acts in the uterus for implantation. The results will provide new knowledge regarding uterine preparation for implantation. The study has considerable implication for developing much-needed diagnostic and therapeutic tools for uterine receptivity and infertility.Read moreRead less
Total Laparoscopic Hysterectomy (TLH) Vs. Total Abdominal Hysterectomy (TAH) For The Treatment Of Endometrial Cancer
Funder
National Health and Medical Research Council
Funding Amount
$809,860.00
Summary
The LACE study is a clinical trial comparing two types of surgery for women with early-stage cancer of the inner lining of the uterus, known as endometrial cancer. Treatment for endometrial cancer involves removal of the uterus, tubes, ovaries and lymph nodes. Traditionally this has been performed by open surgery via an abdominal incision. Open surgery is effective for endometrial cancer, but it is highly invasive, resulting in visible scarring, tissue damage, blood loss and a fairly high risk o ....The LACE study is a clinical trial comparing two types of surgery for women with early-stage cancer of the inner lining of the uterus, known as endometrial cancer. Treatment for endometrial cancer involves removal of the uterus, tubes, ovaries and lymph nodes. Traditionally this has been performed by open surgery via an abdominal incision. Open surgery is effective for endometrial cancer, but it is highly invasive, resulting in visible scarring, tissue damage, blood loss and a fairly high risk of complications. Laparoscopic surgery, commonly referred to as keyhole surgery, is a new approach to removing the uterus, tubes, ovaries and lymph nodes. Preliminary results from this less invasive surgery have been extremely encouraging. Laparoscopic surgery is practical and safe in treating endometrial cancer, while also resulting in less tissue damage, lower blood loss, less pain and a shorter recovery period in hospital. The LACE study aims to give definitive answers about the results offered by laparoscopic surgery in treating women with early stage endometrial cancer. The primary aim is to investigate whether the treatment of endometrial cancer using laparoscopic surgery is as good as that using open surgery. Secondary aims look at whether laparoscopic surgery provides more benefits compared to open surgery for endometrial cancer, such as: - improvements in the quality of life post-surgery, - reduced number of early and late surgery-related complications, - shorter stays in hospital, - fewer blood transfusions required, - less pain post-surgery, and hence fewer pain-killers. The LACE study is already under way, with recruitment on target for Stage 1. This application seeks funding for Stage 2, to expand recruitment from 2007. The outcomes of the trial will have a significant bearing on the future choice of treatment for endometrial cancer. Therefore the study will impact many patients around the world, including ~2000 women every year in Australia.Read moreRead less
Inhibiting Mutant FGFR2 In Endometrial Cancer By Extracellular Blockade
Funder
National Health and Medical Research Council
Funding Amount
$354,859.00
Summary
Endometrial cancer is a common gynecological cancer in women and new therapies are required to improve survival rates. We have identified mutations in a key cell membrane protein (FGFR2) and shown that endometrial cancer cells with these mutations have altered growth factor dependence. Inhibiting these mutant proteins can result in cell death. By characterizing these mutations and their cellular effects we will be able to develop specific blocking agents for use as potential novel treatments
Novel Roles For Follistatin In Reproductive Biology
Funder
National Health and Medical Research Council
Funding Amount
$630,916.00
Summary
The follistatin protein has important functions throughout the body. Recent studies using mutant mice have identified key roles for follistatin in the development and function of the female reproductive system (ovary, uterus). We will now undertake detailed studies to determine how follistatin regulates these processes. This is relevant to our understanding of the mechanisms causing infection and inflammation in the reproductive tract.
Identification And Characterisation Of Cells With High Proliferative Potential In Human Endometrium
Funder
National Health and Medical Research Council
Funding Amount
$409,575.00
Summary
Each month when the uterine lining does not receive an implanting embryo, this lining is shed as part of the menstrual process. It is rapidly replaced with a new functional lining that grows from the basal layer that remains. In post menopausal women, who only have the thin basal layer of the uterine lining, there is rapid regeneration of the lining when they commence hormone replacement therapy. Despite this remarkable regenerative capacity of the uterine lining, nothing is known about the prec ....Each month when the uterine lining does not receive an implanting embryo, this lining is shed as part of the menstrual process. It is rapidly replaced with a new functional lining that grows from the basal layer that remains. In post menopausal women, who only have the thin basal layer of the uterine lining, there is rapid regeneration of the lining when they commence hormone replacement therapy. Despite this remarkable regenerative capacity of the uterine lining, nothing is known about the precursor cells responsible for its cyclical growth. Our preliminary studies have shown that the human uterine lining contains a rare population of cells with high proliferative capacity. This project will identify, characterize and locate these precursor cells in the human uterine lining. It also aims to obtain information on how these precursor cells function in regenerating the uterine lining, how they interact with sex hormones and how their proliferative activity is regulated. Information generated from this project will provide significant new insight into the functioning of the uterine lining. It also has immediate application to common gynaecological diseases associated with abnormal growth of the uterine lining, such as endometriosis, a disease which affects 10% of reproductive age women causing pain and infertility. A better understanding of how these precursor cells may be involved in endometriosis and other gynaecological diseases may ultimately lead to the development of improved medical treatments rather than surgical intervention, which is currently the main form of treatment.Read moreRead less
A Genome-wide Association Study Of Endometrial Cancer
Funder
National Health and Medical Research Council
Funding Amount
$1,066,328.00
Summary
Endometrial cancer (uterine-womb cancer) is the most common invasive gynaecological cancer in Australia. Each year more than 1400 women are affected by the condition. The non-biased approach of our large study will identify genes that increase risk of this cancer, to provide information for future targeted therapies to prevent progression, and large-scale studies investigating how these genes interact with environmental factors such as hormone replacement therapy and obesity to cause disease.