Cancer protein 'can be disarmed'

Scientists have found a way to disarm a protein thought to play a key role in leukaemia and other cancers.

The breakthrough raises hopes of a new type of therapy that could treat cancer and other diseases.

Previous attempts to neutralise the protein had failed, leading experts to conclude it was effectively "undruggable".

The study, carried out by the US Dana-Farber Cancer Institute, features in the journal Nature.

The protein is one of the body's transcription factors, which turn genes on or off and set in motion genetic cascades that control how cells grow and develop. They also help fuel the growth of tumours.

The transcription factor targeted in the latest study is a protein called Notch.

The gene responsible for manufacturing the protein is often damaged or mutated in patients with a form of blood cancer known as T-cell acute lymphoblastic leukaemia (ALL).

Stapled peptides promise to significantly expand the range of what's considered 'druggable' Professor Greg Verdine Dana-Farber Cancer Institute

As a result the gene is switched on all the time, driving the uncontrolled cell growth characteristic of cancer.

Similar abnormalities in Notch also underlie other cancers, including lung, ovarian, pancreatic and gastrointestinal tumours.

Examining the structure of Notch closely, the researchers isolated a potential weak spot in its structure.

They employed a state-of-the-art technique using chemical braces to mould protein snippets called peptides into specific three dimensional shapes.

These "stapled" peptides are readily absorbed by cells, and are so tiny they can be deployed to alter gene regulation at specific sites.

After designing and testing several synthetic stapled peptides, the researchers identified one that was able to disrupt Notch's function.

When tested in mice it was found to limit the growth of cancer cells.

It may lead to alternative drugs and better treatments for this kind of leukaemia and maybe other cancers Dr David Ish-Horowicz Cancer Research UK

Analysis showed that activity was depressed in genes both directly and indirectly controlled by Notch.

The researchers hope the technique could also be used to target other transcription factors with a similar structure.

Researcher Professor Greg Verdine said: "Stapled peptides promise to significantly expand the range of what's considered 'druggable'.

"With our discovery, we've declared open season on transcription factors and other intractable drug targets."

Dr David Ish-Horowicz, head of developmental genetics at Cancer Research UK's London Research Institute, described the research as "very interesting".

He said: "There is already considerable work by scientists into ways to block Notch to try and reverse the effects of ALL, but the current drugs have some serious side-effects.

"This study describes the design of a new chemical that blocks the mechanism in a different way.

"The new chemical has only been tested in mice so far, and so we don't know how it will behave in humans.

"But, long term, it may lead to alternative drugs and better treatments for this kind of leukaemia and maybe other cancers."

http://news.bbc.co.uk/1/hi/health/8353229.stm

Cancer can spread to foetus from the mother

Scientists have established beyond doubt that in rare cases cancer can be transmitted in the womb, following the birth of a baby to a woman with leukaemia.

A team at the Institute of Cancer Research, a college of the University of London, working with colleagues in Japan, found that the cancer had defied accepted theories of biology. Leukaemia cells had crossed the placenta and spread from the 28-year-old mother to her unborn baby.

Dr Tony Ford on how cancer can pass from the woman to foetus in the womb Link to this audio

There have been suspicions for years that cancer could be passed on in the womb. About 17 cases of suspected mother-to-child transmission have been noted – usually leukaemia or melanoma. But until now researchers have been unable to establish whether it had happened and, if so, how.

If the cells did cross the placental barrier, the child's immune system should have recognised them as foreign invaders and destroyed them.

In the latest case no one knew the mother, who was Japanese, had cancer during her pregnancy. She had a normal delivery in hospital, giving birth to an apparently healthy baby girl.

But just over a month later the mother developed vaginal bleeding, which became uncontrollable. She was diagnosed with an advanced stage of leukaemia and died.

When the baby was 11 months old she was brought to hospital with a swollen right cheek. Tests showed she had a tumour in her jaw and the cancer had spread to her lungs.

Although the cancers were not the same – the baby had a lymphoma and is now in remission – the Japanese doctors suspected a link to the leukaemia that had killed her mother.

They called in the team at the Institute of Cancer Research, which has done a lot of work in recent years on the genetics of cancers of identical twins. In the journal Proceedings of the National Academy of Sciences, the researchers explain how they used genetic "fingerprinting" techniques to establish that the child's cancer cells came from the mother.

They found the cancer cells of mother and baby carried the identical mutated cancer gene (called BCR-ABL1), but the infant had not inherited this gene. This meant that the child could not have developed the cancer in isolation – the cells must have come from the mother.

To investigate how leukaemia cells could have crossed the placental barrier and survived in the baby, the scientists looked for evidence of some form of immunological acceptance or tolerance of the foreign cells by the foetus. They examined the genes of the cancer cells in the infant and found a deletion mutation – some DNA missing in the region that controls expression of the major histocompatibility locus (HLA).

This was significant because HLA molecules primarily distinguish one individual, and his or her cells, from another, so the absence of these on the cancer cells meant the infant's immune system would not have recognised that they were foreign.

Professor Mel Greaves, who led the study, said: "It appears that in this and, we presume, other cases of mother-to-offspring cancer, the maternal cancer cells did cross the placenta into the developing foetus and succeeded in implanting because they were invisible to the immune system. We are pleased to have resolved this longstanding puzzle.

"But we stress … the chances of any pregnant woman with cancer passing it on to her child are remote."

Dr David Grant, scientific director at Leukaemia Research, said: "The important message from this … is that leukaemia cells can be destroyed by the immune system. Harnessing the power of the immune system to cure and protect patients from leukaemia is one of our priority areas of research."

http://www.guardian.co.uk/science/2009/oct/12/cancer-passed-from-mother-foetus

Oestrogen can be used to treat breast cancer

While estrogen-lowering drugs are currently used to treat breast cancer, a new study shows that estrogen itself can fight the tumor in those suffering a comeback.

Previous studies had reported that drugs such as tamoxifen and the aromatase inhibitors can treat breast malignancy through cutting off the estrogen required for feeding the estrogen-receptor-positive tumors.

According to the study published in the Journal of the American Medical Association, a very low dose of estrogen can treat relapses in 30 percent of women on estrogen-blocking drugs.

It is also reported to be more effective and much better tolerated than chemotherapy.

Failure, however, is noted in 30 percent of those who had previously responded to the treatment. The study, however, showed that going back on the aromatase inhibitors could stop the progression of the cancer in one third of these patients.

"We demonstrated clearly that the low dose was better tolerated than the high dose and was just as effective for controlling metastatic disease," said lead researcher Matthew Ellis.

He added that a high dose of the drug may cause headaches, bloating, breast tenderness, fluid retention, nausea and vomiting.

Scientists concluded that estrogen can be used to treat metastatic hormone-dependent breast cancer in postmenopausal women.

http://www.presstv.ir/detail.aspx?id=103942&sectionid=3510210

The relevant research papers from the journal can be accessed here:

Estradiol in Breast Cancer Treatment: http://jama.ama-assn.org/cgi/content/extract/302/7/797
Lower-Dose vs High-Dose Oral Estradiol Therapy of Hormone Receptor–Positive, Aromatase Inhibitor–Resistant Advanced Breast Cancer: http://jama.ama-assn.org/cgi/content/short/302/7/774?home

Vegetarians more likely to get colorectal cancer?!

A recent BBC article concerning a recent research into cancer epidemiology was titled: Vegetarians 'get fewer cancers'. While this is well known and universally accepted, the BBC neglected to clearly inform the general public of a more important discovery: Although vegetarians are less likely to get cancer in general, they are significantly more likely to get colorectal cancer!

All those who ever did a module on cancer are left sratching their heads saying WTF?!! What we were taught back in Uni was that carnivorous humans were more likely to get colorectal cancer (amongst other related health issues), but this discovery sheds new light on the subject. The thing we all must be wondering is WHY?

We all know why-not - beneficial phytochemicals, anti-oxidants, the effect on the bacterial flora (positive), lots of fibre promotes healthy bowel movement and reduces cancer-promoting irritation... but now we are wondering - why does it highten the risk of colorectal cancer? Could it be the insecticides - doubtful. Could it be the more dangerous phytochemicals - maybe? Could it be the effect on the bacterial flora (negative)? We just don't know and it really is a shock to be honest. However, there's still the inkling that the data might not be right, that further research may turn this discovery on its head again, or that what was discovered is not a universal response... we shall see in due time.

Anyway, the best advice is to stick to a mostly vegetarian diet as it will help save you from a whole load of problems the heavy meat eaters deal with. Getting just colorectal cancer rather than a whole slew of other cancers and other diseases should be worth it. Your 5 fruit and veg a day target is well worth it so stick to it. Keep Healthy :)