Flinders Medical Centre Foundation
Flinders Medical Centre Foundation



Oxygen's Role in Cancer Spread

Volunteer Service Supports Fresh Ideas

Research To Prevent Renal Transplant Rejection

Easing The Pain Of Kidney Stones

Drug Induced Kidney Damage - Who Is At Risk?



Oxygen's Role in Cancer Spread
First Published: Southern Area Health Service news - April 2011

A Flinders Medical Centre kidney specialist is embarking on a new study to understand how oxygen-depleted cancer cells survive by hijacking and manipulating the body's good cells.

Conducted by Flinders Consultant Nephrologist Professor Jonathan Gleadle, the one-year research project will examine the way in which breast and renal cancer cells develop despite a lack of essential oxygen, a condition known as hypoxia.

According to Jonathan, oxygen is vital for the health of all cells in the body, whether cancerous or not.

He said cells produce small spherical structures called 'exosomes' which send messages to other cells and, in cases of cancer, affect the behaviour of tumours.

Jonathan said the study, funded through a $12,000 grant from the FMC Foundation, would investigate how hypoxic cells respond to low oxygen by communicating with exosomes in a bid to source oxygen.

"We're interested to know whether cancerous cells send out more exosomes when they're starved of oxygen and message other cells to help them," he said.

"While these exosomes probably play a part in the normal body, it seems that in cancer they might get hijacked or have a role in communicating with other cells to support the cancer."

He said it was important to understand not only the behaviour of malignant cells but also the role of healthy cells in facilitating cancer.

"When you're a cancer cell you don't just overtake normal cells - you need their help to survive, whether that be for attracting blood vessels, providing nutrition or manipulating the immune system to prevent it recognising cancer cells.

"If you look at cancer under a microscope, a lot of the cells are cancer cells but there are many different types of normal cells there too.

"So it's important to understand why normal cells are present in a cancerous tumour and the role they play in facilitating that tumour."

He said the study was also significant because the most hypoxic cancer cells often resulted in the worst patient outcomes.

While it remains unclear why hypoxic cancer cells are the most deadly, Jonathan said one explanation could be that hypoxic tumour cells grow differently and act more aggressively. 

"We think this basic and fundamental work examining breast and renal cancer cells will lead to a better understanding of how cancers develop.

"And the support of the Lyn Wrigley Breast Cancer Research and Development Fund, along with the assistance from the FMC Foundation, is crucial for establishing new avenues for research such as this."



Volunteer Service Supports Fresh Ideas
First Published: Investigator - February 2008


Thanks to the hard-working Volunteer Service for Flinders Medical Centre Inc. two bright young minds now have the means to pursue PhDs in groundbreaking fields.


Lauren Thurgood, one of two new Volunteer Service scholarship holders dedicates her time to researching the causes of kidney stones. Her doctorate is on how proteins help to control kidney stones, a field in which Flinders is leading internationally.


As an honours student Ms Thurgood was part of the research team led by Professor Rosemary Ryall who received a $1.2 million grant from the US National Institutes of Health in 2004. They were the first to discover and publish the existence of proteins inside the minerals, predominately calcium oxalate, which cause kidney stones when they attach to kidney cells.


Ms Thurgood hopes to build on this research by identifying the proteins within the crystals, and look at what effects single proteins have on the attachment of the crystals to the kidney cells.


She hopes her research will one day have clinical implications for preventing the formation of kidney stones.


Likewise, scholarship recipient Vicki Edwards is building on the research of Biological Scientists Dr Kirsten Benkendorff and Dr Catherine Abbott, who sought to harness the anti-cancer potential of a local species of sea snail.


It has been found the bioactive compounds involved in the Dicathais orbita or Australian Dogwhelk’s production of a purple dye have many possible medicinal uses, including a novel anti-cancer agent.


Under the supervision of Dr Fiona Young in Medical Biotechnology, Ms Edwards’ doctorate builds on “promising” research by Dr Benkendorff and Dr Abbott into the effects of the compounds on lymphoma and colorectal cancer cells.


Ms Edwards hopes to determine whether the compounds can also kill reproductive cancer cells, or whether they can have an effect on gynaecological conditions caused by hormonal imbalances such as endometriosis and polycystic ovary syndrome.


She also hopes to investigate the viability of a homeopathic treatment for uterine cancer, Murex Purpurea, which has an active ingredient sourced from the same family of mollusc as the Australian Dogwhelk.


At present the Volunteer Service for FMC Inc. provides $194,000 annually to support medical research grants and have recently increased their support to provide for these two new PhD scholarships.


Research To Prevent Renal Transplant Rejection
First Published: Investigator - April 2005


Advanced renal failure carries a very high risk of death from heart attack and stroke.


Amongst other abnormalities in blood chemicals and hormones, patients with renal failure often have a hardening of their arterial vessels which, in turn, increase the blood pressure causing further damage to the kidneys.


The Flinders Medical Centre Foundation has provided funding to Flinders Department of Clinical Pharmacology for a pilot study aimed to investigate the effects of renal transplantation on the stiffening of the arterial vessels.


Renal transplant patients will be studied before and after the transplant operation to see if they show minimal change or significant improvement in their vascular outcome.


Through this study Drs Arduino Mangoni and Jeff Barbara hope to be able to identify vascular changes if any, just after transplant and therefore be in a better position to identify those at risk.


‘Unfortunately some renal transplant patients have some degree of early vascular disease with a high risk of rejection later on. If we can pick them up at an early stage, rejection may be prevented’, said Dr Mangoni.


“We will measure the stiffness of the vessels before and shortly after the operation with a simple, safe and non invasive test. This will assist us to better identify and characterize those patients showing minimal change or improvement in stiffness post-transplant. Some people do well, some people not so well. We want to see if different degrees of improvement of the transplant could be predicted for late rejection”


Dr Mangoni’s project will hopefully lead to a larger project to test the hypothesis that arterial stiffness is an independent predictor of renal transplant rejection.


Easing The Pain Of Kidney Stones
First Published: Investigator - July 2004


If you suffer kidney stones you know just how painful they can be.


As an honours student Ms Thurgood was part of the research team led by Professor Rosemary Ryall who received a $1.2 million grant from the US National Institutes of Health in 2004. They were the first to discover and publish the existence of proteins inside the minerals, predominately calcium oxalate, which cause kidney stones when they attach to kidney cells.


Researchers at Flinders are working towards finding out just how kidney stones form and how they can be prevented.


A Flinders research team, led by Chief Medical Scientist, Professor Rosemary Ryall from the Department of Urology has been awarded a $1.2m grant by the major funding body for medical science in the United States, the National Institute of Health (NIH).


The focus of the ground breaking research is on the formation of insoluble crystals of calcium oxalate found in kidney stones. These crystals commonly appear in urine but are harmlessly excreted from the body most of the time.


Occasionally the process goes wrong and the ureter (the tube that links the kidney and bladder) becomes blocked, causing back pressure on the kidney and resulting in pain and discomfort.


Professor Ryalls’ previous research has discovered that proteins are found in the crystals when they form in the urine. This new NIH funding will allow Rosemary to investigate the role of proteins and how they make the crystals more susceptible to being broken down in the body.


It is thought these proteins encourage proteases (proteins that eat other proteins) to break down unwanted proteins and destroy the crystal structure.


Drug Induced Kidney Damage - Who Is At Risk?
First Published: Investigator - April 2004


Between one and five percent of people taking non-steroidal anti-inflammatory drugs (NSAIDs), used to treat inflammation and provide pain relief, will develop changes in kidney function.


NSAIDs are one of the most commonly administered groups of drugs worldwide and are used in treating many conditions, including rheumatoid arthritis, many sporting injuries and minor aches and pains.


Although NSAIDs pose little threat of kidney damage in healthy people, for those at risk a small percentage may suffer renal failure.


It is widely known that some people taking NSAIDs develop changes in renal function.


Associate Professor Kathie Knights and PhD student Voula Tsoutsikos from the Department of Clinical Pharmacology are working towards identifying how NSAID caused changes in normal renal function. They will also look at who might be at risk of NSAID-induced renal damage as a result of taking these drugs.


Changes can be as simple as fluid and salt retention right through to the more serious problem of acute renal failure. Some renal changes can occur within a week or kidneys may develop damage over a longer period of time. Fortunately these changes in kidney function are usually reversible if NSAID therapy is stopped.


NSAIDs work by blocking the production of prostaglandins (hormone-like substances that trigger pain signals to the brain and bring on inflammation). In some people prostaglandins are also involved in maintaining renal blood flow. The use of an NSAID, which inhibits the production of prostaglandins, may stop your inflammation but at the same time it stops the production of protective prostaglandins in the kidney.


Associate Professor Kathie Knights is hoping to identify a specific marker in those people with normal kidney function who might be at a particular risk of developing renal problems.


"If we can identify those factors within the kidney that increases a person’s risk then there is the potential to design better drugs and to take a different approach in using them."


"I believe we are on the track to identifying a much bigger role that the kidneys have in the metabolism of these drugs. Also the role that the kidneys play in the metabolism of the chemicals which regulate renal function and how NSAIDs actually interfere with these processes", said Assoc Prof Knights.

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