A Simple Blood Test May Catch Early Pancreatic Cancer

A robot processes patient blood samples for evaluation with the CancerSEEK test.
FRED DUBS, JOHNS HOPKINS MEDICAL PATHOLOGY PHOTOGRAPH

Currently, the disease is usually found too late to save lives

Reporting on a small preliminary study, Johns Hopkins researchers say a simple blood test based on detection of tiny epigenetic alterations may reveal the earliest signs of pancreatic cancer, a disease that is nearly always fatal because it isn’t usually discovered until it has spread to other parts of the body.

The findings of their research, if confirmed, they say, could be an important step in reducing mortality from the cancer, which has an overall five-year survival rate of less than 5 percent and has seen few improvements in survival over the last three decades.

“We have mammograms to screen for breast cancer and colonoscopies for colon cancer but we have had nothing to help us screen for pancreatic cancer,” says Nita Ahuja, M.D., an associate professor of surgery, oncology and urology at the Johns Hopkins University School of Medicine and leader of the study described online this month in the journal Clinical Cancer Research. “While far from perfect, we think we have found an early detection marker for pancreatic cancer that may allow us to locate and attack the disease at a much earlier stage than we usually do.”

For their study, Ahuja and her colleagues were able to identify two genes, BNC1 and ADAMTS1, which together were detectable in 81 percent of blood samples from 42 people with early-stage pancreatic cancer, but not in patients without the disease or in patients with a history of pancreatitis, a risk factor for pancreatic cancer. By contrast, the commonly used PSA antigen test for prostate cancer only picks up about 20 percent of prostate cancers.

Ahuja and her colleagues found that in pancreatic cancer cells, it appears that chemical alterations to BNC1 and ADAMTS1 — epigenetic modifications that alter the way the genes function without changing the underlying DNA sequence — silence the genes and prevent them from making their protein product, the role of which is not well-understood. These alterations are caused by the addition of a methyl group to the DNA.

Using a very sensitive method called Methylation on Beads (MOB) developed by Jeff Tza-Huei Wang, Ph.D., a professor at the Whiting School of Engineering at Johns Hopkins, the researchers were able to single out, in the blood, even the smallest strands of DNA of those two genes with their added methyl groups. The technique uses nanoparticle magnets to latch on to the few molecules being shed by the tumors, which are enough to signal the presence of pancreatic cancer in the body, the researchers found.

Specifically, researchers say, they found BNC1 and ADAMTS1 in 97 percent of tissues from early-stage invasive pancreatic cancers. Surgery is the best chance for survival in pancreatic cancer, because radiation and chemotherapy are not very effective against it. The smaller the cancer — the earlier it is detected — the more likely surgery will be successful and the patient will survive.

Ahuja says the practical value of any blood test for cancer markers depends critically on its sensitivity, meaning the proportion of tumors it detects, and its specificity, meaning how many of the positive results are false alarms. The specificity of this new pair of markers is 85 percent, meaning 15 percent would be false alarms. Ahuja says she hopes further research will help refine the test, possibly by adding another gene or two, in order to go over 90 percent in both sensitivity and specificity.

Ahuja also cautions that her team still needs to duplicate the results in a larger sample of tumors, but is encouraged by the results so far. She says she doesn’t envision the blood test as a means of screening the general population, the way mammograms and colonoscopies are used to find early breast and colon cancers. Instead, she imagines it would be best used in people at high risk for developing the disease, such as those with a family history of pancreatic cancer, a previous case of pancreatitis, long-term smokers or people with the BRCA gene mutations, which are linked to breast, ovarian and pancreatic cancers.

“You have to optimize your medical resources,” says Ahuja, who hopes a commercial blood test might one day only cost $50.

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Turning Algae into Clean Energy and Fish Food; Helping Africans to Irrigate Crops

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Could algae that feast on wastewater produce clean bio-fuels and a healthful supply of fish food?

Can impoverished African community gardeners learn to use and maintain a simple centuries-old, non-electric water pump to grow more vegetables?

Two Johns Hopkins student teams are working hard to move these “green” ideas off the drawing board and into the real world. Both teams will showcase their progress at the 2013National Sustainable Design Expo, scheduled April 18 and 19, in Washington, D.C. The event, which will be open to the public on the National Mall, is sponsored by the U.S. Environmental Protection Agency, which provided $15,000 initial grants to each of the Johns Hopkins teams and to more than 40 other students groups that will also participate.

During the Expo, student teams will compete for follow-up grants of up to $90,000 to bring their concepts closer to real-world applications. The awards are part of an EPA program called P3: People, Prosperity and Planet Student Design Competition for Sustainability.

One of the Johns Hopkins student projects focuses on growing large masses of algae to address three sustainability issues: pollution control, the limited supply of fossil fuels and production of healthy food. This team, dubbed AlgaFuture, is composed of undergraduates and graduate students from the departments of Geography and Environmental Engineeringand Chemical and Biomolecular Engineering. Their goal is to deploy algae at wastewater treatment facilities to feed on hard-to-remove pollutants such as nitrogen and phosphorus, which are found in human and animal waste and in agricultural runoff containing fertilizer. If algae can flourish while dining on these pollutants, the plant-like organisms could then be used to produce renewable bio-fuels or food for fish farms.

But the process is not as simple as it sounds. “Wastewater can contain pathogens and dangerous metals like mercury, chromium and arsenic,” said Pavlo Bohutskyi, an environmental engineering doctoral student and leader of this team. “If algae grow in these materials and then are eaten by fish, is it safe for us to eat these fish?”

At the same time, the pathogens in wastewater, such as viruses, fungi and bacteria, could destroy the algae themselves and thwart the plans to produce biofuels and fish food. With an initial EPA grant, the student team tested 20 species of algae. “We found two strains that can grow well alongside pathogens and one that is already present in wastewater samples,” Bohutskyi said.

If the team receives one of the additional EPA grants, he said, the students plan to do further studies to see whether fish food or biofuel production is the most economically viable use for algae grown in wastewater. Their faculty advisers are Edward Bouwer, professor and chair of the Department of Geography and Environmental Engineering, and Michael Betenbaugh, professor in the Department of Chemical and Biomolecular Engineering. Both departments are within the university’s Whiting School of Engineering.

The other Johns Hopkins team aims to improve the irrigation of vegetable gardens that provide nutrition and income for families in remote rural communities in South Africa. In these areas, women and children often spend hours each day hauling heavy containers of water from the local stream for drinking and to water crop-growing sites up to a half-mile away.

Since 2006, students with the Johns Hopkins chapter of Engineers Without Borders-USA (EWB-USA) have journeyed to Africa to help install low-cost ram pumps, devices that date back to the 1700s and do not require electricity or fuel. Instead, they use the kinetic energy of flowing stream water to power the lifting of a fraction of this water to a higher elevation. The process eliminates hand-carrying water and provides much needed irrigation water for the cultivation of winter vegetables. In an additional effort aimed at sustaining the benefits from the EWB-USA effort, a team of undergraduate and graduate environmental engineering students obtained an initial EPA grant to develop a new understanding of pump performance and repair and to help plan sustainable “service centers.” The goal is to enable the community gardeners to maintain and repair their pumps. The focus is on a particularly inexpensive, appropriate and robust type of ram pump designed by a South African named David Alcock.

“We’re working on detailed descriptions of the pump parts and how the pump can be assembled and how it can operate most efficiently,” said Emily Prosser, an undergraduate environmental engineering student who is helping to lead the team. Dano Wilusz, a graduate student member, has been assisting with the plans for the project’s next phase. He added, “We’ve also been working with the Johns HopkinsCarey Business School and South African partners to plan different types of government-supported service centers that could provide advice, spare parts and other help to the community in running these irrigation systems. It’s important because the water allows the farmers to grow more vegetables during dry seasons for their own use and for sale to others.”

If this team is awarded one of the EPA’s follow-up grants, the funds will be used to help open and evaluate two of the proposed service centers in South Africa. The students’ long-range goal is to create a model sustainability program that could be used to enable farmers and community gardeners in other regions to run their own ram pump irrigations systems without relying on outside assistance.

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via Johns Hopkins & Newswise
 

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Cancer Data in the ‘Cloud’ Could Lead to More Effective Treatment

The goal is to help doctors make better predictions about how a patient’s illness will progress and what type of treatment will be most effective.

Storing music and photos on distant computers via “cloud” technology is nothing new. But Johns Hopkins researchers are now using this tactic to collect detailed information from thousands of cancer cell samples. The goal is to help doctors make better predictions about how a patient’s illness will progress and what type of treatment will be most effective.

The project, supported by a new $3.75 million National Cancer Institute grant, was launched because researchers now realize that cancer cells affecting the same type of tissue can behave differently in different patients. Prostate cancers may grow rapidly in one patient, but expand at a glacial pace in another. A drug that kills a tumor in one patient may be useless or even harmful in the next patient.

To help doctors prepare a more personalized medical prognosis and treatment plan, Johns Hopkins has assembled experts in cancer and engineering, led by Denis Wirtz, associate director of the university’s Institute for NanoBioTechnology. The team has begun characterizing and storing cancer data collected through a process called high-throughput cell phenotyping.

“We use scanning microscopy to take pictures of the size and shape of cancer cells,” said Wirtz, who also directs the Johns Hopkins Physical Sciences-Oncology Center. “We also extract information about what is happening inside the cells and at the genetic level. We make notes of the age and gender of the patient and any treatment received. Looked at as a whole, this information can help us identify a ‘signature’ for a certain type of cancer.

That gives us a better idea of how it spreads and how it responds to certain drugs.”
He added, “The long-range goal is to make this data available through the Internet to physicians who are diagnosing and treating cancer patients around the world.”

Wirtz, a professor of chemical and biomolecular engineering in the university’s Whiting School of Engineering, has been working with School of Medicine researchers Ralph Hruban and Anirban Maitra to begin the database with material from the files of thousands of cancer patients who have been evaluated and treated at Johns Hopkins. The patients’ personal information has been deleted, but the remaining medical case data allows the researchers to trace the course of the disease from initial testing through treatment and outcome.

“This technology may provide a way to centralize specimen data, images and analysis in a way that hasn’t been done before,” said Maitra, a professor of pathology and oncology, “and we’ll be using the information now to find better ways to treat disease.”

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via Johns Hopkins University

 

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Computational Medicine Begins to Enhance the Way Doctors Detect and Treat Disease

Many challenges must still be overcome before computational medicine becomes a routine part of patient care

Computational medicine, a fast-growing method of using computer models and sophisticated software to figure out how disease develops–and how to thwart it–has begun to leap off the drawing board and land in the hands of doctors who treat patients for heart ailments, cancer and other illnesses. Using digital tools, researchers have begun to use experimental and clinical data to build models that can unravel complex medical mysteries.

These are some of the conclusions of a new review of the field published in the Oct. 31 issue of the journal Science Translational Medicine. The article, “Computational Medicine: Translating Models to Clinical Care,” was written by four Johns Hopkins professors affiliated with the university’s Institute for Computational Medicine.

The institute was launched in 2005 as collaboration between the university’s Whiting School of Engineering and its School of Medicine. The goal was to use powerful computers to analyze and mathematically model disease mechanisms. The results were to be used to help predict who is at risk of developing a disease and to determine how to treat it more effectively.

In recent years, “The field has exploded. There is a whole new community of people being trained in mathematics, computer science and engineering, and they are being cross-trained in biology,” said institute director Raimond Winslow. “This allows them to bring a whole new perspective to medical diagnosis and treatment. Engineers traditionally construct models of the systems they are designing. In our case, we’re building computational models of what we trying to study, which is disease.”

Looking at disease through the lens of traditional biology is like trying to assemble a very complex jigsaw puzzle with a huge number of pieces, he said. The result can be a very incomplete picture. “Computational medicine can help you see how the pieces of the puzzle fit together to give a more holistic picture,” Winslow said. “We may never have all of the missing pieces, but we’ll wind up with a much clearer view of what causes disease and how to treat it.”

Biology in both health and disease is very complex, Winslow added. It involves the feed-forward flow of information from the level of the gene to protein, networks, cells, organs and organ systems. This is already complex, he said, and to make matters even more difficult, it also involves feed-back pathways by which, for example, proteins, mechanical forces at the level of tissues and organs, and environmental factors regulate function at lower levels such as the gene.

Computational models, Winslow said, help us to understand these complex interactions, the nature of which is often highly complex and non-intuitive. Models like these allow researchers to understand disease mechanisms, aid in diagnosis, and test the effectiveness of different therapies. By using computer models, he said, potential therapies can be tested “In Silico” at high speed.  The results can then be used to guide further experiments to gather new data to refine the models until they are highly predictive.

“Our intent in writing this journal article was to open the eyes of physicians and medical researchers who are unfamiliar with the field of computational medicine,” said Winslow, who is first author of the Science Translational Medicine overview. He also wanted to describe examples of computational medicine that are making their way out of research labs and into clinics where patients are being treated. “This transition,” he said, “is already under way.”

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