Over-expressed protein may make non-invasive breast cancer invasive

Washington, Sep 9 (ANI): An over-expressed protein can convert active but non-invasive breast cancer into a different cell type, and thereby turn it into invasive breast cancer, according to scientists at The University of Texas M. D. Anderson Cancer Center.

The researchers say that overexpression of the protein 14-3-3? (zeta) launches a molecular cascade that removes bonds that tie the pre-malignant cells together, and hold them in place, converting them from stationary epithelial cells to highly mobile mesenchymal-like cells.

This epithelial-to-mesenchymal transition (EMT) is recognized as a crucial step in metastasis, the spread of cancer to distant organs that causes 90 percent of all cancer deaths.

“We have discovered a key molecular mechanism for the deadly transition of non-invasive breast cancer into invasive disease,” said senior author Dr. Dihua Yu.

The researchers have shown that the zeta protein teams up with the oncoprotein ErbB2, also known as HER2, in a two-hit process to convert normal mammary cells to invasive cancer cells.

The findings of the study also provided a biomarker in zeta to identify high-risk patients for more aggressive treatment before their noninvasive breast cancer converts to invasive disease.

The researchers also got new therapeutic targets among the components of the molecular pathway launched by zeta.

According to Yu, some drugs already aim at these targets.

In addition, they found a solution to a puzzling mystery about how a subset of non-invasive breast cancer with excessive presence of an ErbB2/HER2 develops into invasive breast cancer.

Earlier, the researchers showed that zeta is over-expressed in many other cancer types, like lung, liver, uterine, stomach cancers.

“Our findings might have broader implications relating to the mechanism of invasion and metastasis in other types of cancer,” Yu said.

The researchers said that it would be very challenging to target zeta by drugs because it also regulates other important proteins in normal cellular processes.

The study has been published in the journal Cancer Cell. (ANI)

How diarrhoeal bacteria may cause some colon cancers

London, August 24 (ANI): Johns Hopkins scientists have gained significant insights into how bacteria that cause diarrhoea may also be responsible for some colon cancers.

The researchers have found that strains of the common Bacteroides fragilis (ETBF) dupe immune system cells into permitting runaway colon tissue inflammation, a precursor for malignant growth.

“This could be the H. pylori of colon cancer,” Nature magazine quoted Dr. Cynthia Sears, Johns Hopkins infectious disease specialist, as saying, referring to the bacteria long known to cause stomach ulcers and suspected of causing the majority of stomach cancers.

During the study, she and her colleagues observed that ETBF uses tissue inflammation to cause colon cancer in a similar way that H. pylori causes stomach tumours.

In their study report, the researchers have highlighted the fact that a so-called enterotoxigenic bacterium is widely known to cause diarrhoea in children and adults, and that a previous study in Turkey has linked it to colon cancer.

While the bacteria does not cause any symptoms in some individuals, others develop diarrhoea and colon inflammation, which has been linked to cancer growth.

Unlike the case with H. pylori, it is unknown whether standard antibiotics can eradicate the microbe, experts say.

With a view to finding the link between ETBF and colon cancer, the researchers conducted a series of tests in mice bred to carry mutations in a colon cancer-causing gene called APC.

They observed that mice infected with ETBF developed diarrhoea that resolved quickly, but within a week, the animals developed inflammation and small tumours in the colon.

One month later, the colons were pockmarked with tumours.

Mice infected with a non-toxin producing strain of the bacteria were free of diarrhoea, inflammation, and tumours.

While evaluating the bacteria’s effect on immune responses that may contribute to cancer development, the researchers observed that in ETBF-infected mice, there were high levels of a protein called pStat3, which, in its normal role, acts as a signal to trigger inflammation.

One of those signals activates an immune cell called T-helper 17 (Th17). Th17 cells produce molecules that have been implicated in fostering inflammation of tissues.

The researchers said that Th17 activity in the gut of germ-bearing mice was 100 times greater than normal, and when it was blocked, inflammation and tumour growth in the animals was reversed.

Dr. Drew Pardoll, an immunologist and cancer researcher at Johns Hopkins, speculates that in humans, infection with ETBF “produces a low-level inflammation that persists for a long time.”

“If what we are seeing in mice holds true in humans, the chronic inflammation damages genetic material in the colon cells, allowing them to grow uncontrollably and develop into tumors earlier and more progressively than if they were not infected with ETBF,” Pardoll says.

Sears and Pardoll believe that ETBF may collude with other types of normal bacteria in the gut to promote cancer.

Given that the microbe itself is difficult to culture from stool specimens, th eresearchers are working on blood tests to detect antibodies to the pathogen’s toxin, which may show whether an individual has been exposed to it and perhaps determine who may be at risk for colon cancer.

The investigators also envision vaccines and drug therapies that neutralize the pathogen’s toxin and its ability to inflame tissues.

The study has been published in the journal Nature Medicine. (ANI)

Drinking very hot tea ‘raises throat cancer risk’

London, Mar 27 (ANI): Follow your mum’s advice and drink tea five to ten minutes after making, for a new study has found, steaming tea increases the risk of throat cancer.

The British Medical Journal research claims that drinking very hot tea (70 degree Celsius or more) can raise the risk of cancer of the oesophagus, the muscular tube that carries food from the throat to the stomach.

Cancers of the oesophagus kill more than 500,000 people worldwide each year and oesophageal squamous cell carcinoma (OSCC) is the commonest type.

To reach the conclusion, researchers studied tea-drinking habits among 300 Iranians with OSCC and a matched group of 571 healthy controls from the same area.

Nearly all participants drank black tea regularly. Compared with drinking warm or lukewarm tea, drinking hot tea was associated with twice the risk of oesophageal cancer, and drinking very hot tea was associated with eight-fold increased risk.

Likewise, compared with drinking tea four or more minutes after being poured, drinking tea less than two minutes after pouring was associated with a five-fold higher risk.

There was no association between the amount of tea consumed and risk of cancer. (ANI)