Protein Found in Blood Might Help Detect Lung Cancer Sooner: Report

Preliminary finding focused on non-small cell lung cancer, Chinese researchers say

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New test aims to better detect viral infections

WASHINGTON (AP) — It happens too often: A doctor isn't sure what's causing someone's feverish illness but prescribes antibiotics just in case, drugs that don't work if a virus is the real culprit.

Now Duke University researchers are developing a blood test to more easily tell when a respiratory illness is due to a virus and not a bacterial infection, hoping to cut the dangerous overuse of antibiotics and speed the right diagnosis.

It works by taking a fingerprint of your immune system — how its genes are revving up to fight the bug. That's very different from how infections are diagnosed today. And if the experimental test pans out, it also promises to help doctors track brand-new threats, like the next flu pandemic or that mysterious MERS virus that has erupted in the Middle East.

That viral "signature could be quite powerful, and may be a game-changer," said Dr. Geoffrey Ginsburg, Duke's genomic medicine chief. He leads the team that on Wednesday reported that a study involving 102 people provided early evidence that the test can work.

Today, when symptoms alone aren't enough for diagnosis, a doctor's suspicion guides what tests are performed — tests that work by hunting for evidence of a specific pathogen. Fever and cough? If it's flu season, you might be tested for the flu virus. An awful sore throat? Chances are you'll get checked for strep bacteria. A negative test can leave the doctor wondering what germ to check for next, or whether to make a best guess.

Moreover, rapid in-the-office tests aren't always accurate and can miss infections. So patients may have blood or other samples sent to labs to try to grow any lurking bacteria and tell if it's to blame, additional testing that can take days.

"This is something we struggle with every day," said Dr. Octavio Ramilo, infectious disease chief at Nationwide Children's Hospital in Columbus, Ohio, who wasn't involved in the new study. Particularly with children, a respiratory virus and a bacterial infection "in the beginning look completely alike," he added.

Hence researchers at a number of universities are trying to harness a fairly recent discovery: As your immune system detects an invading bug, different genes are activated to fend off a viral infection than to fight a bacterial or fungal one. Those subtle molecular changes appear to be occurring even before you feel any symptoms. And they form distinct patterns of RNA and proteins, what's called a genomic fingerprint.

The Duke team discovered 30 genes that are switched on in different ways during a viral attack. The test essentially is a freeze-frame to show "what those genes are doing at the moment in time that it's captured," explained Duke lead researcher Dr. Aimee Zaas, an infectious disease specialist.

Small studies spotted that viral signature in people who volunteered to be infected with different influenza strains for science.

For a more real-world simulation, the researchers then analyzed blood samples stored from feverish people who had come to the emergency room — and who were eventually diagnosed, the old-fashioned way, with either some type of virus or a bacterial infection.

The genomic test proved 89 percent accurate in sorting out who had a virus, and did even better at ruling out those who didn't, Zaas reported Wednesday in the journal Science Translational Medicine.

It took 12 hours to get results. The researchers hope to speed that up so that it might work as quickly as some in-office tests.

Still, "it's a promising tool," said Ramilo, an Ohio State University professor who is doing similar research. He called the Duke study an important step toward creating a commercial test, and predicts one might reach the market within five years.

Why would a doctor want to know merely that a virus is present and not which virus? That's enough information to rule out antibiotics, Zaas said. Unnecessary antibiotic use is one factor in the growing problem of drug-resistant germs, which the government blames for more than 23,000 deaths a year.

Plus, if a dangerous new virus begins spreading, like MERS, this approach could help avoid quarantining people unnecessarily by telling right away which ones are virus-free, Ginsburg added.

In Ohio, Ramilo is exploring a more immediate need: When young infants have high fevers, they're often hospitalized while doctors run a battery of tests to find the fraction who have a serious bacterial infection. He is leading a study involving 22 pediatric emergency rooms to see if a genomic fingerprint approach could separate which babies really need all that testing.

But the virus-or-not question is just the beginning, Ramilo said. His research suggests genomic fingerprints also can distinguish a flu strain from other common viruses. And the Duke team is analyzing a huge study of students living in dormitories, to see if the genomic test detected who was incubating the flu before their first sniffle — and thus might be useful in stemming outbreaks.

Copyright c 2013 The Associated Press. All rights reserved. This material may not be published, broadcast, rewritten or redistributed.

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Protein Found in Blood Might Help Detect Lung Cancer Sooner: Report

TUESDAY, Sept. 17 (HealthDay News) -- A protein that can be detected using a noninvasive blood test might one day help aid in the early diagnosis of lung cancer, preliminary research suggests.

A study conducted by researchers in China found that people with lung cancer have high levels of the so-called "biomarker," isocitrate dehydrogenase (IDH1). The investigators pointed out that lung cancer is the leading cause of cancer deaths in both men and women in the United States and around the world, and diagnosing the disease sooner could help reduce its high mortality rate.

"This study is the first to report identification of IDH1 as a novel biomarker for the diagnosis of non-small cell lung cancers using a large number of clinical samples," Dr. Jie He, director of the laboratory of thoracic surgery at the Peking Union Medical College and Chinese Academy of Medical Sciences in Beijing, said in a news release from the American Association for Cancer Research.

"Lung cancer has a high mortality rate, mostly because of late diagnosis. With an increase in aging population, we are likely to see an increase in lung cancer incidence and a need for better biomarkers for early diagnosis. We have identified IDH1 as an effective plasma [blood] biomarker with high sensitivity and specificity in the diagnosis of [non-small cell lung cancer]," He continued, especially the type known as lung adenocarcinoma.

The study, published in the current issue of the journal Clinical Cancer Research, involved blood samples collected from 943 patients with non-small cell lung cancers and 479 people who did not have lung cancer (the "control" group). None of the patients was diagnosed or treated for cancer in the three years before the study began.

The study found that the median IDH1 levels in patients with lung adenocarcinoma were 2.7 times higher than the healthy participants. The levels of this protein were also 2.2 times higher in those with squamous cell carcinoma, compared to the control group.

He's team noted that IDH1 can be detected in the blood of lung cancer patients with 76 percent sensitivity and 77 percent specificity. That means 24 percent of the tests would miss lung cancer, and 23 percent would diagnose lung cancer when it wasn't there. The researchers noted that when combined with current markers used to diagnose lung cancer, the sensitivity increased to 86 percent.

"Based on the present data, IDH1 can be used to detect stage 1 lung cancer; however, it is also possible that IDH1 could be used to detect precancer but further studies are required to address that possibility," added He.

"Our research also suggests IDH1 may be involved in the development of lung cancer, and it may be a good target for the treatment of [non-small cell lung cancer]," said He. The research team is currently studying what causes the increase of IDH1 in lung cancer patients and what the findings mean for patients.

More information

The U.S. National Cancer Institute has more about lung cancer.

Copyright c 2013?HealthDay. All rights reserved.

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Smartphone 'microscope' can detect a single virus, nanoparticles

Sep. 17, 2013 — Your smartphone now can see what the naked eye cannot: A single virus and bits of material less than one-thousandth of the width of a human hair.

Aydogan Ozcan, a professor of electrical engineering and bioengineering at the UCLA Henry Samueli School of Engineering and Applied Science, and his team have created a portable smartphone attachment that can be used to perform sophisticated field testing to detect viruses and bacteria without the need for bulky and expensive microscopes and lab equipment. The device weighs less than half a pound.

"This cellphone-based imaging platform could be used for specific and sensitive detection of sub-wavelength objects, including bacteria and viruses and therefore could enable the practice of nanotechnology and biomedical testing in field settings and even in remote and resource-limited environments," Ozcan said. "These results also constitute the first time that single nanoparticles and viruses have been detected using a cellphone-based, field-portable imaging system."

The new research, published on Sept. 9 in the American Chemical Society's journal ACS Nano, comes on the heels of Ozcan's other recent inventions, including a cellphone camera-enabled sensor for allergens in food products and a smart phone attachment that can conduct common kidney tests.

Capturing clear images of objects as tiny as a single virus or a nanoparticle is difficult because the optical signal strength and contrast are very low for objects that are smaller than the wavelength of light.

In the ACS Nano paper, Ozcan details a fluorescent microscope device fabricated by a 3-D printer that contains a color filter, an external lens and a laser diode. The diode illuminates fluid or solid samples at a steep angle of roughly 75 degrees. This oblique illumination avoids detection of scattered light that would otherwise interfere with the intended fluorescent image.

Using this device, which attaches directly to the camera module on a smartphone, Ozcan's team was able to detect single human cytomegalovirus (HCMV) particles. HCMV is a common virus that can cause birth defects such as deafness and brain damage and can hasten the death of adults who have received organ implants, who are infected with the HIV virus or whose immune systems otherwise have been weakened. A single HCMV particle measures about 150-300 nanometers; a human hair is roughly 100,000 nanometers thick.

In a separate experiment, Ozcan's team also detected nanoparticles -- specially marked fluorescent beads made of polystyrene -- as small as 90-100 nanometers.

To verify these results, researchers in Ozcan's lab used other imaging devices, including a scanning electron microscope and a photon-counting confocal microscope. These experiments confirmed the findings made using the new cellphone-based imaging device.

Ozcan is the principal investigator on the research. The first author of ACS Nano the paper is Qingshan Wei, a postdoctoral researcher in Ozcan's lab and at UCLA's California NanoSystems Institute (CNSI), where Ozcan is associate director. Other co-authors include Hangfei Qi and Ting-Ting Wu of the UCLA Department of Molecular and Medical Pharmacology; Wei Luo, Derek Tseng, Zhe Wan and Zoltan Gorocs of the UCLA Electrical Engineering Department; So Jung Ki of the UCLA Department of Chemistry and Biochemistry; Laurent Bentolila of CNSI and the UCLA Department of Chemistry and Biochemistry; and Ren Sun of the UCLA Department of Molecular and Medical Pharmacology and CNSI.

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New tests to detect drug-resistant malaria

Sep. 10, 2013 — Researchers have developed two tests that can discern within three days whether the malaria parasites in a given patient will be resistant or susceptible to artemisinin, the key drug used to treat malaria. The tests were developed by researchers from the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, working with French and Cambodian colleagues in Cambodia. They offer a more rapid, less costly advantage over current drug-responsiveness tests, which require malaria patients to be hospitalized for blood draws every six hours over the course of several days. In both tests, young parasites are briefly exposed to a high dose of artemisinin, mimicking the way parasites are exposed to the drug in people being treated for malaria, and their survival is measured 72 hours later.

The first test is conducted on blood taken from a malaria patient at the same time as the first dose of artemisinin-based combination drug therapy is administered. The test returns results in 72 hours and can predict whether the patient has slow-clearing, drug-resistant parasites. The researchers note that the simple, new test could be used for surveillance studies to monitor and map the emergence or spread of artemisinin-resistant malaria parasites. In the current study, researchers using this test detected artemisinin-resistant parasites at sites in Northern and Eastern Cambodia for the first time.

The second test is conducted on parasites grown in the laboratory. This test requires trained technicians to adapt parasites from a malaria patient to a laboratory culture, synchronize the life-stages of the parasites, and then apply the drug only to those that are three hours old or younger. This test will likely be most useful in future studies designed to elucidate the molecular basis of artemisinin resistance and to screen new malaria drugs.

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Story Source:

The above story is based on materials provided by NIH/National Institute of Allergy and Infectious Diseases, via EurekAlert!, a service of AAAS.

Note: Materials may be edited for content and length. For further information, please contact the source cited above.

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Journal Reference:

1. Benoit Witkowski, Chanaki Amaratunga, Nimol Khim Msc A, Sokunthea Sreng, Pheaktra Chim, Saorin Kim, Pharath Lim, Sivanna Mao, Chantha Sopha, Baramey Sam, Jennifer M Anderson, Socheat Duong, Char Meng Chuor, Walter R J Taylor, Seila Suon, Odile Mercereau-Puijalon, Dr Rick M Fairhurst, Didier Menard. Novel phenotypic assays for the detection of artemisinin-resistant Plasmodium falciparum malaria in Cambodia: in-vitro and ex-vivo drug-response studies. The Lancet Infectious Diseases, September 2013

Note: If no author is given, the source is cited instead.

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