Flinders Medical Centre Foundation
Flinders Medical Centre Foundation

Colorectal Cancer

Resistant Starch Balances Red Meat Risks

Molecular 'Markers' For Cancer Treatment

New Technology Singles Our Proteins In Prostate Cancer

Improving Screening For Inherited Cancers

Volunteer Service Supports Fresh Ideas

 Bowel Cancer Study

MicroRNA Patent Returns Outstanding Results

Healing Properties of a Common Sea Snail

How Cancers Form Under Investigation

Screening Program Sends a Lifeline To Luke

Do You Have Lymphoedema

Beans Means Healthy Bowels!

Cancer Causing Genes Under The Microscope

Resistant Starch Balances Red Meat Risks
First Published: Investigator - July 2009

Flinders researchers are studying the potential role of a dietary fibre supplement in reducing the risk for bowel cancer in people who consume a diet rich in red meat.

‘The aim of the study is to ascertain whether the consumption of a diet high in red meat causes changes in certain markers for bowel cancer, and whether adding resistant starch to the diet can improve these effects,’ Flinders Cancer Prevention and Control researcher Dr Richard Le Leu, said.

Participants in the study will be asked to consume 300 grams of either beef or lamb daily for a total of eight weeks, interspersed with lower-meat periods. During one of the 4-week red meat phases of the study they will also be asked to take a daily fibre supplement that is high in resistant starch.

‘Scientists have long suspected that a diet high in red meat may contribute to a greater risk of developing bowel cancer. What we want to determine is whether the addition of a resistant starch supplement may help counter this risk,’ Dr Le Leu said.

He said it would be good news for many Australians if it did. ‘Australia has a high consumption of red meat compared to many countries in the world, and we also have a high incidence of bowel cancer. Anything that could reduce that risk would be welcome.’

Participants involved in the study will need to attend a clinic at Flinders Medical Centre on five occasions at 4-weekly intervals.

The study is headed by Professor Graeme Young, the director of Gastroenterology at Flinders Medical Centre (FMC) and involves scientists from the CSIRO. For further information about the study contact study nurse Libby Bambacas on (08) 8204 5534 or study coordinator Jane Upton in the FMC Gastroenterology Unit on (08) 8204 6071.

Molecular ‘Markers’ For Cancer Treatment
First Published: Investigator - May 2009

An internationally-recognised Flinders-led clinical trial has provided proof in principle that molecular ‘markers’ can help predict a response to cancer therapy when treating bowel cancer.

The finding is considered so significant that the study’s principal investigator and primary author, Flinders Medical Centre Medical Oncologist Dr Chris Karapetis was short-listed for The Lancet’s Paper of the Year. The Lancet is one of the world’s best known and most respected peer reviewed medical journals.

Dr Karapetis headed a multi-site randomised clinical trial involving 572 patients from cancer care centres in Australia, Canada, New Zealand and Singapore to test the efficacy of a new monoclonal antibody called cetuximab in treating advanced bowel cancer. This treatment was given following failure of chemotherapy when no other treatment options existed. The antibody was given once per week as a one hour intravenous infusion and the effectiveness was compared to best supportive care, which is optimal palliative care for patients in this situation.

The trial initially found that those patients given cetuximab survived for longer, but the magnitude of benefit was small. The research team then began a retrospective examination to determine which set of patients benefited best from the treatment.

Dr Karapetis coordinated an analysis that examined specific changes in a gene within the cancer cells called KRAS.

‘We knew from previous research that bowel cancer tumours that contain KRAS mutations do not respond, that is shrink, when exposed to cetuximab-based therapy,’ he said.

‘So we examined cancer tissue from each patient and divided them according to the presence or absence of mutations in the KRAS gene. We found that patients with KRAS mutant tumours did not derive any benefit from cetuximab, which is what we predicted, but the survival time for patients with tumours without the KRAS mutation was doubled if they were treated with cetuximab.’

Patients were at end-stage illness, and gained on average an extra 4.5 months. Dr Karapetis said the research would one day lead to molecular ‘profiles’ being established for individual tumours so that patients could receive the most effective treatment, based on their molecular markers, rather than the organ of cancer origin.

New Technology Singles Out Proteins In Prostate Cancer
First Published: Investigator - February 2009

The Newell Foundation, dedicated to supporting prostate cancer research in memory of the late Brian Newell, has donated $10,000 to purchase a 2D electrophoresis kit for the Flinders Proteomics Facility.

The 2D electrophoresis equipment will give researchers the tools to separate the tens of thousands of proteins which are present within cells so that one can be looked at specifically.

It will be used primarily by PhD student Yabin Zhou, who is using proteomics to investigate why the male hormone androgen is involved in prostate cancer.

He hopes to determine what androgen’s link is to a particular protein which has been identified as causing an increased expression of calcium channels in cancerous cells.

Proteomics, the study of proteins which are involved in every part of a cell’s function, is an area of science that has only evolved in the last decade.

In the state-of-the-art Flinders Proteomics Facility, researchers from all fields can compare diseased cells to healthy cells, and identify the differences in the proteins.

It is hoped by identifying those proteins which are more (or less) abundant in diseased cells, they can develop better diagnostic markers and more targeted treatments.

Dr Tim Chataway, Head of the Flinders Proteomics Facility, said proteomics is at the “discovery phase” of research projects.

“Say we wanted to discover a new colorectal cancer bio marker. We might take some normal tissue and colorectal cancer tissues and then extract all the proteins and see which ones are in greater or lesser quantities inside colorectal cancer cells,” he said.

“Once we’ve identified the targets, researchers can then verify those proteins and develop ways to assay or measure them.”

Current projects underway at the Flinders Proteomics Facility include investigations into the role proteins play in degenerative diseases, cancer, eye disease, asthma, kidney stones, and multiple sclerosis, to name but a few.

Improving Screening For Inherited Cancers
First Published: Investigator - August 2008

Important research at Flinders has continued to make inroads into inherited breast and ovarian cancers thanks to a $16,000 contribution from Angela Condous and the Advertiser and Sunday Mail Foundation (ASMF).

Dr Scott Grist and his team are developing a cost-effective pre-screening laboratory test to better identify individuals who may carry a harmful BRCA1 or BRCA2 gene defect.

The BRCA genes are responsible for repairing DNA damage in a cell. If a defect is inherited in one or both genes there is a 60-80% chance that breast or ovarian cancer will develop as DNA damage accumulates over time.

“Approximately 20% of those screened carry DNA variants that cannot be easily identified as those that cause cancer,” said Dr Scott Grist, Head of the Inherited Cancer Genetics Lab at Flinders Medical Centre.

“This represents a large group of individuals with an uncertain diagnosis who are not benefiting from the testing and who are put under additional psychological stress.”

The current screening method is also quite costly, limiting it to those who know they have a strong family history of breast and ovarian cancer.

Using a technique that screens for DNA damage, this test can measure the rate of DNA repair of a possible BRCA gene defect carrier against the rate of repair from a healthy BRCA gene sample.

This will identify if a full screening of the BRCA genes is required, both saving un-necessary and extensive screening and easing the minds of those who don’t know their family’s medical history or have an unknown defect in a BRCA gene.

The ASMF will hold another fundraising lunch on 27 August 2008 to continue raising funds for breast cancer research at Flinders. Contact the Flinders Medical Centre Foundation on (08) 8204 5216 for more information or to book tickets.

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.

Bowel Cancer Study
First Published: Investigator - February 2008

Researchers are seeking people to take part in a study to test the effectiveness of two different selenium supplements which may improve bowel health.

Selenium might not be available in adequate amounts in the diet of Australian people. It is enriched in a few foods such as brazil nuts, some sea foods and the organs of some farm animals including kidneys.

The study will examine the benefits to bowel health of a selenium-enriched dairy milk product and a selenium yeast product. Both products are prepared naturally by feeding selenium supplements to dairy cows.

Professor of Gastroenterology at Flinders Medical Centre and Flinders University. Graeme Young said blood levels of selenium in Australians are barely adequate by international standards which is why dietary supplements could be important in improving bowel health and therefore reducing the risk of bowel disease.

Study participants will consume either the milk or yeast product for a period of six weeks with a follow-on monitored six week period without the selenium product. Blood tests and effects on bowel health will be assessed regularly during each period. 4711.

Volunteers aged greater than 50 years who are interested in taking part in the study can contact Gastroenterology Research Nurse Libby Bambacas on 8204 5534. Entry criteria does apply.

MicroRNA Patent Returns Outstanding Results
First Published: Investigator - July 2007

Flinders Medical Centre (FMC) investigators have received outstanding results on an international Patent application for their research in utilising specific molecules that could lead to better cancer therapies.

Dr Michael Michael and his team have contributed important information into the link between microRNAs and cancer formation, placing them at the forefront of this field of research.

“MicroRNAs were thought to be a quirk of nature when first discovered in nematode worms over a decade ago,” said Dr Michael. “By 2002 it was discovered that these tiny by-products of genes are in fact present in all plants and animals.”

Cells have various functions which are dictated by their proteins. These proteins are, in turn, created by different genes within the cell. MicroRNAs are responsible for targeting and shutting down specific genes where necessary and occasionally stopping the production of a protein that is harmful to the body.

Dr Michael and his team identified two microRNAs (145 and 143) in 2002 that appear in low quantities or are not present at all within cancer cells. This finding could shine light on what happens within a cell for it to turn cancerous while also helping to create better treatments.

Research is a highly competitive field with scientists vying for grants around the world. This can lead to knowledge and technology not being readily shared.

The Patent is still pending, but once awarded, Dr Michael’s microRNA technology can be used by scientists around the world to create better outcomes, not only for cancer but possibly for other diseases.

Healing Properties Of A Common Sea Snail
First Published: Investigator - April 2006

Flinders investigators are currently involved in harnessing the natural anti-cancer property created by a common sea snail which could be used to treat many different forms of cancer.

Dr Kirsten Benkendorff and Dr Catherine Abbott, Lecturers in Biological Sciences at Flinders University, have been investigating this marine snail, the Australian Dogwhelk Dicathais orbita, which is found throughout shallow rocky reef habitats along the southern coast from New South Wales to Western Australia.

This snail produces a purple dye, known as Tyrian purple, which appears to be a means of protecting its egg masses. It has been found that the compounds that produce this dye have many possible medicinal uses, one of these being a potent anti-cancer agent.

This agent appears to cause programmed cell death within cancerous cells, triggering these unwanted cells to self-destruct by shrinking and fragmenting slowly rather than a sudden disintegration that can be harmful to healthy neighbouring cells.

Currently the project is delving into the biological mechanisms that take place within this snail to create the purple dye. It is hoped that part of the process, the anti-cancer agent, can be harnessed and possibly used as a treatment for cancer.

As this project is only in the very early stages much research needs to be undertaken to make sure that biological material such as DNA, metabolic processes, enzymes and the membrane of healthy cells are not harmed or destroyed by using a treatment that utilises this agent.

The next step in this project will be to look at the gastro-protective elements of the snail and to ascertain whether it could be used as a functional food with healing properties, perhaps for colorectal cancers.

Dr Benkendorff is also interested in further investigating homeopathic remedies used for hundreds of years to treat female health issues by testing the healing properties of this snail on reproductive cell lines such as ovarian and breast cancers, and hormone production.

“This is a huge project with exciting potential, particularly as this snail has several interesting biological compounds that haven’t been seen before; this study could provide some very useful information in the treatment of cancers,” says Dr Benkendorff.

How Cancers Form Under Investigation
First Published: Investigator - February 2006

Flinders researchers are leading the world in an area of cancer research that is providing a vital insight as to how cancerous cells may or may not form within the breast and bowel.

Headed by Dr Michael Michael from the Department of Gastroenterology and Hepatology, this research is focused on two specific microRNA’s; tiny products of the genes within our cells.

In 2001 it was discovered that microRNA’s are present in all plants and animals and have the ability to control the formation of proteins within cells. This information took the scientific world by storm when it was realised that this could provide a simpler approach to manipulating genes and therefore altering genetic disorders and diseases, such as cancer.

Each protein within a cell has a specific function causing the cell to act in a certain way, for example grow hair or cause pigmentation. RNA, often called a messenger, helps create these proteins by taking a copy of a sequence of the DNA held within a cell and carrying it into another area of the cell where the protein can be created.

MicroRNAs are involved in the defence against diseases, as they are responsible for controlling the creation of proteins. They are thought to fine-tune delicately balanced processes that control how cells behave. These processes include how the cells mature, divide and move relative to each other. If a microRNA is missing, this could lead to a cascade of events and become deleterious to the cell creating, for example; a cancerous tumour.

Dr Michael and his team have found that microRNA’s 145 and 143 are often in low quantities or not present at all within breast cancer cells – and may be responsible for the disease. This information stemmed from an earlier finding by Dr Michael that microRNA’s 145 and 143 are also not present in bowel cancers.

“These microRNA’s are important for two reasons,” says Dr Michael. “First, they might potentially control the processes that lead to cancer and create better understanding of what is happening within a cancerous cell. And secondly, the potential application to regulate genes in cells may be available for a wide range of disorders.”

Whilst this research is still in the early stages, a possible outcome could be a gene therapy utilising the defensive systems of these microRNA’s and leading to the destruction of cancerous tumours.

Screening Program Sends a Lifeline To Luke
First Published: Investigator - April 2005

Luke Sincock would have never have thought at 22 years of age he was in the high-risk category for bowel cancer.

With a long and detailed family history of bowel cancer involving around 40 family members, Luke was recently delivered a lifeline when a screening program detected early signs of bowel cancer.

The Southern Cooperative Program for the Prevention of Colorectal Cancer (SCOOP) at the Flinders Medical Centre is the brainchild of Professor Graeme Young, a leading researcher in the field, and Dr Peter Bampton, Head of Endoscopy.

“The chances of more than one family member having bowel cancer currently stands at between two to three per cent, so the Sincock family’s situation is extremely rare,” Professor Young said.

“The aim of SCOOP is to ensure that those at high risk of developing bowel cancer have the appropriate tests done at the right time, and then have them repeated at the right interval. We do not want people to forget or be forgotten.

“If the majority of the population were to participate in screening using existing simple stool test technologies, within ten years the death rate from bowel cancer alone would be reduced by 40 per cent.

Professor Young said that in the context of a family risk for bowel cancer, colonoscopies traditionally take place every three to five years, allowing staff to detect abnormalities by viewing the inside of the intestine using a microscopic camera. Occasionally people require colonoscopies more frequently.

“We’ve further enhanced the screening program by introducing a home testing kit, known as faecal immunochemical test (FIT) for the 4,000 or so people currently involved in the program to carry out in between colonoscopies,” he said.

Professor Young says the home test can be used for the general population for screening, or for people with a family history in between colonoscopies.

“This allows us to detect certain abnormalities in the bowel, namely pre-cancerous polyps or early cancers, to be picked up in the curable stages. It is a more discreet and less obtrusive way of checking which reassures both the individual and the clinicians.” .

As an Australian-first, the SCOOP program has already proven to be highly successful and is attracting attention from hospitals around the country.

In his role as Director of Development for the proposed $14.5 million Flinders Centre for Innovation in Cancer, Professor Graeme Young says the Centre will focus on all aspects of prevention, and the SCOOP program is just one example of the type initiative that will be part of this Centre.

Do You Have Lymphoedema?
First Published: Investigator - February 2005

The Flinders Lymphoedema Assessment Clinic is undertaking three large scale clinical trials.

One trial involves the application of an ointment to the arms of women with lymphoedema following treatment for breast cancer.

The second trial involves the use of a new lymphatic vessel stimulatory program to the legs of men and women who have lymphoedema following treatment for cancer of the bowel, reproductive systems, or due to the removal of lymph nodes in the groin associated with melanoma.

The third trial involves the testing of a Tai Chi exercise program - one hour per week for nine weeks for women with arm lymphoedema following treatment for breast cancer.

If you have lymphoedema and would like further information on the Clinic please call 8204 4711.

Beans Means Healthy Bowels!
First Published: Investigator - October 2004

Next time you shop at the supermarket, pick up a can of baked beans because they could be the key to reducing your bowel cancer risk.

A new study at Flinders has confirmed foods high in resistant starch, such as baked beans, rice and pasta, can improve bowel health and reduce the risk of bowel cancer, the most frequently occurring cancer in Australia today.

Most foods are digested in the small intestine but resistant starch resists digestion in the small intestine and reaches the bowel. In the bowel, it is fermented by bacteria, which produce short chain fatty acids. The fatty acids provide a source of energy for colon cells and are proven to be an effective anti cancer agent.

Professor of Gastroenterology at Flinders Medical Centre and Flinders University Graeme Young and Research Fellow Dr Richard Le Leu recently conducted the study using a product high in resistant starch called Hi-Maize® - a food ingredient made from specially bred Australian corn.

The study showed a 30 percent increase in the death of potentially cancerous cells in the colon when the diet included more than 20 percent Hi-Maize.

Death of genetically damaged cells occurs through an automatic biological function called apoptosis. Without apoptosis, the genetically damaged cells could multiply and develop into colorectal cancer. A diet high in resistant starch increases the apoptotic response and may reduce the risk of developing bowel cancer.

A 10 percent Hi Maize diet supplemented with probiotics has also been found to increase apoptotic response. Probiotics are a food ingredient commonly found in yoghurt and fermented milk drinks that deliver external ‘friendly’ bacteria to the gut.

Professor Young and Dr Le Leu now plan to test the resistant starch and combined starch probiotic diet for their effect on colonic tumour development.

Cancer-Causing Genes Under The Microscope
First Published: Investigator - April 2004

A major scientific discovery in 2001 has opened the door for Flinders researchers to further study the genes responsible for the development of colorectal cancer.

European and US scientists working on fields as diverse as worms and plants discovered microRNAs. Found in all animal cells, these molecules have the ability to turn off gene function.

Once thought to be a bit of ‘junk’ MicroRNA's have turned out to be very useful. They play a vital role in the development of various organisms, and are likely to be involved in many human diseases, including cancer.

Dr Michael Michael from the Department of Gastroenterology, believes Flinders is at the leading-edge in studying the microRNA controlled genes that may cause colorectal cancer.

"We are the first to find a correlation between microRNA's and solid tumours. This is novel work. Our lab is one of only a few in the world that have published in this area,” said Dr Michael.

"Although in it's early stages one of the strengths of this research is access to Flinders Tissue Bank. This enhances our ability to discover what causes the changes in gene activity that are associated with many cancers."

It is hoped that by understanding these processes Flinders researchers may be able to develop new diagnostics and cancer treatments.

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