Posts Tagged ‘china’

New method for non-invasive prostate cancer screening

Now a team of researchers led by Shaoxin Li at Guangdong Medical College in China has demonstrated the potential of a new, non-invasive method to screen for prostate cancer, a common type of cancer in men worldwide. They describe their laboratory success testing an existing spectroscopy technique called surface-enhanced Raman scattering (SERS) with a new, sophisticated analysis technique called support vector machine (SVM).

As they described in a new paper in Applied Physics Letters, from AIP Publishing, they combined SERS and SVM and applied them to blood samples collected from 68 healthy volunteers and 93 people who were clinically confirmed to have prostate cancer. They found their technique could identify the cases of cancer with an accuracy of 98.1 percent.

If the technique proves safe and effective in clinical trials, it may become a new method available to patients and their doctors, helping to improve the early detection and diagnosis of this type of cancer, said Li.

“The results demonstrate that label-free serum SERS analysis combined with SVM diagnostic algorithm has great potential for non-invasive prostate cancer screening,” said Li. “Compared to traditional screening methods, this method has the advantages of being non-invasive, highly sensitive and very simple for prostate cancer screening.”


According to the World Health Organization, prostate cancer is one of the most common types of cancer in men worldwide and a leading cause of cancer-related death. Every year, there are about 899,000 new cases and 260,000 mortalities, comprising 6 percent of all cancer deaths globally. About 1 in every 6 men will develop prostate cancer over their lifetimes.

While a simple blood test for elevated levels of a protein marker known as prostate specific antigen (PSA) has been used for years to screen for early cases of prostate cancer, the test is far from perfect because the elevated PSA levels can be caused by many things unrelated to cancer. This contributes to over-diagnosis, uncomfortable tissue biopsies and other unnecessary treatment, which can be costly and carry significant side effects. Because of this, the U.S. Preventative Services Task Force now recommends against PSA-based screening for prostate cancer.

According to Li, many scientists have thought about applying SERS to cancer detection because the surface-sensitive type of spectroscopy has been around for years and is sensitive enough to identify key molecules in very low abundance, like pesticide residues on a contaminated surface. This would seem to make it perfect for spotting subtle signals of DNA, proteins or fatty molecules that would mark a case of cancer — exactly why he and his team tackled the problem.

The challenge, he said, was that these changes were, if anything, too subtle. The signal differences between the serum samples taken from the 68 healthy volunteers and the 93 people with prostate cancer were too tiny to detect. So to accurately distinguish between these samples, Li’s group employed a powerful spectral data processing algorithm, support vector machine (SVM), which effectively showed the difference.

While the work is preliminary, it shows that serum SERS spectroscopy combined with SVM diagnostic algorithm has the potential to be a new method for non-invasive prostate cancer screening, Li said. The next research step, he added, is to refine the method and explore whether this method can distinguish cancer staging.

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Mystery of brain cell growth unraveled by scientists

How a single protein can exert both a push and a pull force to nudge a neuron in the desired direction is a longstanding mystery that has now been solved by scientists from Dana-Farber Cancer Institute and collaborators in Europe and China.

Jia-huai Wang, PhD, who led the work at Dana-Farber and Peking University in Beijing, is a corresponding author of a report published in the August 7 online edition of Neuron that explains how one guidance protein, netrin-1, can either attract or repel a brain cell to steer it along its course. Wang and co-authors at the European Molecular Biology Laboratory (EMBL) in Hamburg, Germany, used X-ray crystallography to reveal the three-dimensional atomic structure of netrin-1 as it bound to a docking molecule, called DCC, on the axon of a neuron. The axon is the long, thin extension of a neuron that connects to other neurons or to muscle cells.

As connections between neurons are established — in the developing brain and throughout life — axons grow out from a neuron and extend through the brain until they reach the neuron they are connecting to. To choose its path, a growing axon senses and reacts to different molecules it encounters along the way. One of these molecules, netrin-1, posed an interesting puzzle: an axon can be both attracted to and repelled from this cue. The axon’s behavior is determined by two types of receptors on its tip: DCC drives attraction, while UNC5 in combination with DCC drives repulsion.

“How netrin works at the molecular level has long been a puzzle in neuroscience field,” said Wang, “We now provide structure evidences that reveal a novel mechanism of this important guidance cue molecule.” The structure showed that netrin-1 binds not to one, but to two DCC molecules. And most surprisingly, it binds those two molecules in different ways.

“Normally a receptor and a signal are like lock-and-key, they have evolved to bind each other and are highly specific — and that’s what we see in one netrin site,” said Meijers. “But the second binding site is a very unusual one, which is not specific for DCC.”

Not all of the second binding site connects directly to a receptor. Instead, in a large portion of the binding interface, it requires small molecules that act as middle-men. These intermediary molecules seem to have a preference for UNC5, so if the axon has both UNC5 and DCC receptors, netrin-1 will bind to one copy of UNC5 via those molecules and the other copy of DCC at the DCC-specific site. This triggers a cascade of events inside the cell that ultimately drives the axon away from the source of netrin-1, author Yan Zhang’s lab at Peking University found. The researchers surmised that, if an axon has only DCC receptors, each netrin-1 molecule binds two DCC molecules, which results in the axon being attracted to netrin-1. “By controlling whether or not UNC5 is present on its tip, an axon can switch from moving toward netrin to moving away from it, weaving through the brain to establish the right connection,” said Zhang.

Knowing how neurons switch from being attracted to netrin to being repelled opens the door to devise ways of activating that switch in other cells that respond to netrin cues, too. For instance, many cancer cells produce netrin to attract growing blood vessels that bring them nourishment and allow the tumor to grow, so switching off that attraction could starve the tumor, or at least prevent it from growing.

On the other hand, when cancers metastasize they often stop being responsive to netrin. In fact, the DCC receptor was first identified as a marker for an aggressive form of colon cancer, and DCC stands for “deleted in colorectal cancer.” Since colorectal cancer cells have no DCC, they are ‘immune’ to the programmed cell death that would normally follow once they move away from the lining of the gut and no longer have access to netrin. As a result, these tumor cells continue to move into the bloodstream, and metastasize to other tissues. “Therefore, to understand the molecular mechanism of how netrin works should also have a good impact in cancer biology,” said Wang.

The guidance issue is a very complicated cell biology problem. Meijers, Zhang, Wang and their colleagues are now investigating how other receptors bind to netrin-1, exactly how the intermediary molecules ‘choose’ their preferred receptor, how other guidance molecule binds to DCC, and how the system is regulated. The answers could one day enable researchers to steer a cell’s response to netrin and other guidance cues, ultimately changing its fate.

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Cell mechanics may hold key to how cancer spreads, recurs

Some particularly enterprising cancer cells can cause a cancer to spread to other organs, called metastasis, or evade treatment to resurface after a patient is thought to be in remission. The Illinois team, along with colleagues in China, found that these so-called tumor-repopulating cells may lurk quietly in stiffer cellular environments, but thrive in a softer space. The results appear in the journal Nature Communications.

“What causes relapse is not clear,” said study leader Ning Wang. Wang is the Leonard C. and Mary Lou Hoeft Professor in Engineering and professor of mechanical science and engineering of the U. of I. “Why are there a few cells left that can come back stronger? We thought cancer cells may have some properties in common with stem cells, which allows them to metastasize to different tissues. Normally, if you take a liver cell and put it in your lung, it will die. But an undifferentiated cell will live.”

Two years ago, Wang’s group published a method for selecting tumor-repopulating cells (TRCs) from a culture. Thanks to this selection method, the researchers isolated and studied TRCs from melanoma, an aggressive skin cancer notorious for spreading and recurring, to see how the mechanical environment around the cells affected their ability to multiply and cause new tumors.

The researchers grew the cells on gels of different stiffnesses — some very soft and some more firm, to mimic different types of tissues in the body. What they found surprised them.

The TRCs placed in very soft gels grew and multiplied, as expected. The cells placed on stiffer gels did not proliferate; however, they did not die, either — they became dormant. When the researchers later transferred the dormant TRCs to a soft gel, the cells “woke up” and began to multiply and spread.

Wang speculates that these properties of dormancy and reawakening when the mechanical environment is more inviting may explain why soft tissues, such as the brain or lungs, are most vulnerable to metastasis.

“We have many different types of organs where solid tumors originate, but if you look at the metastasized sites, the majority are in soft tissues,” said Wang. “Brain, lung, liver and bone marrow, all soft. So it may not be coincidence. We need to do more research.”

Next, Wang and colleagues hope to tackle the question of what makes TRCs so resistant to drugs, a trait that makes recurrent cancer much harder to treat. Unlocking this puzzle may help doctors fight recurrent cancer, although Wang hopes that understanding how TRCs work can lead to treatments that prevent metastasis in the first place.

“The key issue in this paper is outlining the mechanisms that control how TRCs proliferate,” Wang said. “The importance of knowing these mechanisms is that we now have targets that we didn’t have before, specific targets for new types of drugs that will interfere with this renewal pathway. It could give us a new avenue for treatment and preventing relapse.”

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