Bowel cancer 'could be fuelled by E coli stomach bug'

One of Britain’s most common cancers could be fuelled by the E coli stomach bug, scientists believe.

The breakthrough raises the prospect of a vaccine against bowel cancer, which claims 16,000 lives a year and is the second most common form of the disease in women after breast cancer and the third most diagnosed in men.

The elderly, who are most at risk of the bowel cancer, could also be screened for the ‘sticky’ strain of E coli that makes a DNA-damaging poison.

Tests showed Ecoli bacteria to be much more common in bowel cancer patients than in healthy people

Although the idea that a bug is involved in cancer might seem strange, it is not unheard of, with a virus being to blame for most cases of cervical cancer and a bacterium strongly linked to stomach cancer.

Now, tests on mice and people, carried out in the UK and US, have pointed to E coli being a strong suspect in bowel cancer.

The concern surrounds a version that sticks well to the inside of the lower bowel, or colon.  It also contains genes that make a poison which causes the type of damage to DNA usually seen in cancer.

Although we usually think of E coli as causing food poisoning, these strains had been thought to live in the bowel without causing any problems.

However, tests show them to be much more common in bowel cancer patients than in healthy people.

Two-thirds of the 21 samples taken from bowel cancer patients contained the bug, compared to just one in five of those taken from healthy people, the journal Science reports.

Experiments also showed that  mice inoculated with the bug are at very high odds of developing bowel cancer – as long as the E coli carries the poison-making ‘pks’ genes.

Liverpool University’s Dr Barry Campbell, a co-author of the study, said: ‘The research suggests that Ecoli has a much wider involvement in the development of colon cancer than previously thought.

‘It is important to build on these findings to understand why this type of bacteria, containing the pks genes, is present in some people and not in others.’

Professor Jonathan Rhodes said: ‘The bottom line message is that there seems to be a strong association between a type of E coli and the development of colon cancer.

‘And given that this type of E coli is specifically able to damage DNA and inflict the sort of damage you get in a cancer, it is very likely it has a causative role, at least in some patients.’

The scientists, who collaborated with scientists from the University of North Carolina, aren’t sure why some people who have the bug go onto develop cancer and others don’t.

But factors such as genes and diet are probably important.

Professor Rhodes said: ‘The literature on colon cancer taken as a whole suggests that having the right genes, taking exercise, possibly taking an aspirin a day, limiting red meat and eating plenty of leafy green vegetables all have a protective effect.’

If the link is confirmed, it could lead to tests for the rogue form of E coli being included in bowel cancer screening for the elderly.

In the long-term, a vaccine that stops the bug from taking root is also possible, added the professor.

There is a precedent for this – the HPV vaccine which is given to teenage girls wards off infection by the human papilloma virus - the bug behind the majority of cases of cervical cancer.

Henry Scowcroft, of Cancer Research UK, said: ‘This is an intriguing study in mice suggesting that the bacteria in our gut may play a role in the development of bowel cancer. 

‘This would make sense, as we know that being infected with bacteria called H pylori can increase the chances of developing stomach cancer. 

‘But since this study only involved mice and is still at an early stage, it’s not yet clear whether E coli is actually linked to bowel cancer in humans at all, let alone whether this knowledge could be used to help improve things for patients or people at risk.’

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Drug could attack ‘the root’ of cancer cells: study

The findings, published in the journal Cell, have yet to be proven in humans and clinical trials may reveal thioridazine is not effective at treating cancer. 

But the initial discovery is creating excitement among cancer experts who have been looking for ways to target cancer stem cells. 

Until the 1990s, scientists didn’t know such a thing as cancer stem cells existed. They assumed cancer arose from ordinary cells that have somehow mutated. 

But some scientists turned their attention to stem cells – which have the ability to become any tissue type and multiply infinitely. They postulated that abnormal stem cells are the real culprits behind the growth of many tumours. 

Researchers, including cancer stem cell pioneer and Toronto scientist John Dick, identified their presence in leukemia, breast cancer, brain cancer, lung cancer and other types of cancers. 

Those findings suggested that cancer stem cells are a subset of regular cancer cells that act as the “starter” agents that can cause tumours to grow and cancerous cells to propagate. Scientists believe they help explain why some patients don’t respond to chemotherapy or radiation; those treatments kill cancer cells, but don’t get to the source of the problem. 

Mick Bhatia, lead author of the new study and scientific director of the Stem Cell and Cancer Research Institute at McMaster University in Hamilton, Ont., likened it to cutting dandelions. 

“Unless you eliminate the root, it’s just going to come back,” he said. 

Dr. Bhatia and his colleagues decided to look for treatments that could target cancer stem cells. They developed a system to test dozens of drugs on cancer stem cells and normal, healthy cells. 

It was an extremely challenging task because it required the research team to figure out a way to properly isolate cancer stem cells and healthy stem cells and have them grow outside the body. They found that thioridazine worked at killing the cancer stem cells in leukemia and some types of breast cancer, but left the healthy cells unharmed. The researchers then took cancerous tissue from humans and transplanted it into mice. Once again, thioridazine was effective at targeting the cancer stem cells. 

The reason the drug seems to work is that it affects the dopamine receptor in cancer stem cells. Most cells don’t have a dopamine receptor, and Dr. Bhatia said it was surprising to find it in cancer stem cells. It’s possible that cancer stem cells evolved to develop a dopamine receptor pathway, allowing them to propagate without the body being able to stop them. 

Now, the next step is to test the drug in human clinical trials to determine how well it works. Researchers hope to test the drug on cancer patients who have not responded to traditional treatments such as standard chemotherapy. If it turns out to work, thioridazine might be used in a wider group of cancer patients. 

“If they do respond and we can increase quality of life and potentially even get rid of the cancer, I think it’s the best thing anyone can hope for,” Dr. Bhatia said. 

The research team will also continue to test more compounds – Dr. Bhatia hopes to look at thousands – to find more that are effective at fighting cancer stem cells. He said the research team has already identified about a dozen other compounds that could also attack cancer stem cells and leave healthy cells unharmed. 

Health Canada ordered thioridazine off the market in Canada in 2005 following reports it could increase the risk of rare, but potentially fatal, changes in heart rhythm. 

Dr. Bhatia noted that heart problems typically occur in patients taking thioridazine for a prolonged period; cancer patients would be on it for only a matter of days or weeks. But it’s important to study how the drug works in cancer patients, he said, in order to determine what side effects may occur.

Cadmium in diet is linked to higher breast cancer risk.

             

In a finding that strengthens the link between environmental pollutants and rising rates of breast cancer, new research finds that women whose diets contain higher levels of cadmium are at greater risk of developing breast cancer than those who ingest less of the industrial chemical in their food.

Cadmium, a heavy metal long identified as a carcinogen, leaches into crops from fertilizers and when rainfall or sewage sludge deposit it onto farmland. Whole grains, potatoes, other vegetables and shellfish are key dietary sources of cadmium, which also becomes airborne as a pollutant when fossil fuels are burned, and is likely inhaled as well as ingested.

The new study, published by the American Assn. for Cancer Research and released Thursday, found that among 55,987 post-menopausal women, the one-third with the highest cadmium intakes were 21% more likely to develop breast cancer than the one-third with the lowest intakes.

Among obese women, the study found no increase in breast cancer rates with higher cadmium exposures.

The study offers new evidence in a large human population that environmental chemicals that mimic the effects of the female hormone estrogen may contribute to women's risk of certain cancers, including endometrial and breast cancers.

The finding comes just three months after the Institute of Medicine, a prestigious body of independent biomedical researchers, concluded that a host of other factors — most within a woman's power to control, such as obesity and hormone-replacement medication — were the most important sources of breast cancer risk.

The panel of experts had called it "biologically plausible" that estrogen-like pollutants promote breast cancers, but noted that evidence that they contribute significantly was inconclusive. By contrast, studies in human populations strongly point to fattening foods, hormone-replacement drugs, alcohol and cigarettes as having roles in boosting a woman's breast cancer risk.

Even this study, while showing a correlation, did not prove cause and effect, experts noted.

UC Davis epidemiologist Irva Hertz-Picciotto, chairwoman of the Institute of Medicine panel that issued its findings in December, said the study "does not move us beyond" the panel's overall conclusions.

"At this point, we have not identified the major drivers of the increase in breast cancer," Hertz-Picciotto said. If cadmium pollution truly turns out to be a cause, she added, "it's probably a small part" of a very large picture.

Each year, about 230,000 women in the United States are newly diagnosed with invasive breast cancer. Breast cancer rates are rising worldwide, with 1.6 million cases in 2010.

A woman's lifetime exposure to estrogen — a hormone made by her own body and present in medications such as birth control pills and hormone-replacement treatments — powerfully influences her risk. In animals and in laboratory tests, cadmium has been shown to exert estrogen-like effects more powerfully than other environmental pollutants, and so suspicion has fallen on the heavy metal as a possible promoter of breast cancer.

"Cadmium is receiving a lot of attention these days because of its estrogenic properties," said Rudolph Rull, a research scientist at the Cancer Prevention Institute of California in Berkeley.

But Rull, who was not involved in the current study but is researching cadmium's effects, said that scientists were unsure how best to measure women's exposure to the chemical. That fact, he said, had made it difficult to show whether and how strongly it might drive cancer incidence.

The current study gauged ingested cadmium only. It estimated a woman's exposure to the chemical on the basis of food logs, extrapolating her likely dietary exposure to cadmium on the basis of national estimates of cadmium in crops.

Looking for a link between dietary cadmium and breast cancer is tricky enough for researchers. But for women who have increased their intake of whole grains and vegetables in hopes that doing so will ward off cancers, finding such a link poses a difficult dilemma: Should they eat fewer of those?

"I wouldn't recommend to anyone to stop eating vegetables and whole grains," Hertz-Picciotto said. "If you were to sit down and do cost-benefit analysis, my intuition is you wouldn't want to sacrifice the great benefits that we already know about and are quite well established for what at this point needs to be looked at in greater detail."

The latest research follows two other studies, published in 2006 and 2010, that first singled out cadmium as a factor in breast cancer. Those studies measured cadmium in the urine of smaller groups of pre- and post-menopausal women, and found that those who had high cadmium exposures were more than twice as likely to develop breast cancer as those with the smallest exposures.

In 2010, consumer watchdog groups warned that toys and costume jewelry manufactured in China and marketed to children throughout the United States contained high levels of cadmium, as well as lead.

New wonder-drug for neuro and endocrine cancers.

 

The Amrita Centre for Nanosciences in Cochin on Tuesday unveiled what is said to be a wonder drug to treat neuro-endocrine tumours.

The product has been developed at the Amrita Centre by a team headed by Manzoor Koyakutty. Amrita Centre belongs to Mata Amritananda Mayi.

The drug, Nanophotomedicine, was launched at a three-day conference organised by the Amrita Centre for Nanosciences that began here Tuesday.

According to Koyakutty, the nanomedicine for neuro-endocrine tumours can eliminate tumour cells much more efficiently than the available therapies by better targeting the cancer cells.

'Wonder drug' to wipe out cancer is here.

Scientists claim to have achieved a major breakthrough by creating a 'wonder drug' which kills off cancer -- in fact, it could wipe out some of the most deadly forms of the disease.   

An international team, led by University of California, says that the KG5 drug works by making cancer cells "commit suicide"; it stops tumorous cells multiplying and they then shut themselves down, the 'Nature Medicine' journal reported.

The radical drug will bring fresh hope to patients with aggressive and deadly tumours and could be available in as little as five years, say the scientists, who hope to deliver the it in pill form, which has very few side-effects. 

Lead scientist Prof David Cheresh said the drug "blocks the function of proliferation" and the malignant cells commit suicide when they can't multiply. Proved effective in tests against pancreatic, breast and kidney cancers, it could well have a positive effect on a broad range of other tumours.

KG5 works in a totally different way to traditional therapies by altering the structure of a cancer growth protein, an enzyme known as RAF.

The protein has been long-studied, but its role in cell division -- critical to cell proliferation and tumour growth -- is a surprise. Existing treatments block RAF's activity. However, KG5 changes the entire shape of the protein, which neutralises it without leading to unwanted side-effects. To date, KG5 has been tested in animals and tissue samples taken from patients.

The team has since developed variants of KG5 that are 100-fold more powerful than the original drug. They hope one of these more powerful compounds will enter clinical trials on humans at Moores Cancer Center in San Diego within 18 months.

"Before this drug was designed, we had no idea RAF could promote tumour cell cycle progression. This may be only one example of how, by designing drugs that avoid the active site of an enzyme, we can identify new and unexpected ways to disrupt the growth of tumours.

"In essence, we are attacking an important enzyme in a whole new way and thereby discovering new things this enzyme was intended for," the 'Daily Express' quoted Prof Cheresh.

At present, medicines that target enzymes like RAF often damage healthy cells, according to Prof Cheresh. "They hit many different targets, meaning they can produce undesired side-effects and induce dose-limiting toxicity," he said.

Rather than homing in on a particular part of the protein, the new class of RAF inhibitor alters the enzyme's whole structure. It singles out RAF in proliferating cells, while ignoring normal or resting cells. KG5 also acts by cutting off the blood supply to tumours.

Stop Signal Discovered for Skin Cancer

Developing SCC on the skin. Cells are growing in an uncontrolled fashion after damaging the tumour suppressor.

In research recently published in the cancer journal, Cancer Cell, an international team of scientists led by Professor Stephen Jane and Dr Charbel Darido of Monash University's Department of Medicine at the Alfred Hospital, has discovered a gene that helps protect the body from squamous cell cancer (SCC) of the skin.     

The Cancer Council estimates that two in three Australians will be diagnosed with skin cancer before the age of 70 with SCC being one of the most common forms. Up until now, its genetic basis has not been well understood, with surgical treatments the only option.

Professor Jane said the team discovered that a gene with an important role in skin development in the fetus is missing in adult SCC tumor cells. Although the researchers initially focused on skin cancer, they found that the protective gene is also lost in SCC that arises in other tissues, including head and neck cancers, that are often associated with a very poor outcome for the patient.

"Virtually every SCC tumor we looked at had almost undetectable levels of this particular gene, so its absence is a very profound driver of these cancers," Professor Jane said.

In collaboration with Associate Professor Rick Pearson from the Peter MacCallum Cancer Center, the Monash researchers showed that loss of this particular gene knocks out the signal to stop skin cells from growing. Without this stop signal, the cells keep increasing in number and eventually forms a cancer.

Identifying this driver of cancer in skin and other organs provides a clear direction for developing strategies for both prevention and treatment in the relatively near future.

"Our research indicates that drugs already in clinical trials for other cancers may actually be effective in treating SCC -- they just need to be applied to skin or head and neck cancers.

"This means that a number of the usual hurdles in getting therapies to trial have already been cleared, so patients could be reaping the benefits of this research in under five years," Professor Jane said.

"It's a similar case with prevention. There are strategies by which we could increase the expression of this gene that will likely afford some protection from skin cancer, for example in the form of a supplement in sun-cream. The molecules that would increase this expression, are very well validated, so there would be few barriers to applying them in clinical trials."