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Posts Tagged ‘John McDonald Ph.D.’

Outside-the-Body Filtration Device May Reduce Ovarian Cancer Cells In Abdominal Fluid

Posted by Paul Cacciatore on January 27, 2011

A paper published in the January issue of the journal Nanomedicine could provide the foundation for a new ovarian cancer treatment option — one that would use an outside-the-body filtration device to remove a large portion of the free-floating cancer cells that often create secondary tumors.

Schematic shows how fluids containing ovarian cancer cells could be removed from the body, treated with magnetic nanoparticles to remove the cells, then returned to the body. (Courtesy of Ken Scarberry)

Magnetic nanoparticles suspended in a liquid are attracted to a magnet. The nanoparticles could be attached to cancer cells and then removed from the body with magnetic filtration. (Credit: Gary Meek)

A paper published in the January issue of the journal Nanomedicine could provide the foundation for a new ovarian cancer treatment option — one that would use an outside-the-body filtration device to remove a large portion of the free-floating cancer cells that often create secondary tumors.

Researchers at the Georgia Institute of Technology have formed a startup company and are working with a medical device firm to design a prototype treatment system that would use magnetic nanoparticles engineered to capture cancer cells. Added to fluids removed from a patient’s abdomen, the magnetic nanoparticles would latch onto the free-floating cancer cells, allowing both the nanoparticles and cancer cells to be removed by magnetic filters before the fluids are returned to the patient’s body.

In mice with free-floating ovarian cancer cells, a single treatment with an early prototype of the nanoparticle-magnetic filtration system captured enough of the cancer cells that the treated mice lived nearly a third longer than untreated ones. The researchers expect multiple treatments to extend the longevity benefit, though additional research will be needed to document that — and determine the best treatment options.

“Almost no one dies from primary ovarian cancer,” said Dr. John McDonald, a professor in Georgia Tech’s School of Biology and chief research scientist of Atlanta’s Ovarian Cancer Institute. “You can remove the primary cancer, but the problem is metastasis. A good deal of the metastasis in ovarian cancer comes from cancer cells sloughing off into the abdominal cavity and spreading the disease that way.”

The removal system being developed by McDonald and postdoctoral fellow Ken Scarberry — who is also CEO of startup company Sub-Micro — should slow tumor progression in humans. It may reduce the number of free-floating cancer cells enough that other treatments, and the body’s own immune system, could keep the disease under control.

Professor John McDonald (standing) and postdoctoral fellow Ken Scarberry examine statistical data from their study of a potential new treatment option for ovarian cancer. (Credit: Gary Meek)

“If you can reduce metastasis, you can improve the lifespan of the person with the disease and get a better chance of treating it effectively,” said McDonald. “One goal is to make cancer a chronic disease that can be effectively treated over an extended period of time. If we can’t cure it, perhaps we can help people to live with it.”

Earlier in vitro studies published by the authors of the Nanomedicine paper showed that the magnetic nanoparticles could selectively remove human ovarian cancer cells from ascites fluid, which builds up in the peritoneal cavities of ovarian cancer patients. The nanoparticles are engineered with ligands that allow them to selectively attach to cancer cells.

The researchers believe that treating fluid removed from the body avoids potential toxicity problems that could result from introducing the nanoparticles into the body, though further studies are needed to confirm that the treatment would have no adverse effects.

The recently reported study in Nanomedicine used three sets of female mice to study the benefit of the nanoparticle-magnetic filtration system. Each mouse was injected with approximately 500,000 murine ovarian cancer cells, which multiply rapidly — each cell doubling within approximately 15 hours.

In the experimental group, the researchers — who included research scientist Roman Mezencev — removed fluid from the abdomens of the mice immediately after injection of the cancer cells. They then added the magnetic nanoparticles to the fluid, allowed them to mix, then magnetically removed the nanoparticles along with the attached cancer cells before returning the fluid. The steps were repeated six times for each mouse.

One control group received no treatment at all, while a second control group underwent the same treatment as the experimental group — but without the magnetic nanoparticles. Mice in the two control groups survived a median of 37 days, while the treated mice lived 12 days longer — a 32 percent increase in longevity.

Though much more research must be done before the technique can be tested in humans, McDonald and Scarberry envision a system very similar to what kidney dialysis patients now use, but with a buffer solution circulated through the peritoneal cavity to pick up the cancer cells.

“What we are developing is akin to hemofiltration or peritoneal dialysis in which the patient could come into a clinic and be hooked up to the device a couple of times a week,” said Scarberry. “The treatment is not heavily invasive, so it could be repeated often.”

The new treatment could be used in conjunction with existing chemotherapy and radiation. Reducing the number of free-floating cancer cells could allow a reduction in chemotherapy, which often has debilitating side effects, Scarberry said. The new treatment system could be used to capture spilled cancer cells immediately after surgery on a primary tumor.

The researchers hope to have a prototype circulation and filtration device ready for testing within three years. After that will come studies into the best treatment regimen, examining such issues as the number of magnetic nanoparticles to use, the number of treatments and treatment spacing. If those are successful, the company will work with the FDA to design human clinical trials.

The researchers also studying how their magnetic nanoparticles could be engineered to capture ovarian cancer stem cells, which are not affected by existing chemotherapy. Removing those cells could help eliminate a potent source of new cancer cells.

The research has been supported by the Georgia Research Alliance (GRA), the Ovarian Cancer Institute, the Robinson Family Foundation and the Deborah Nash Harris Endowment. A member of Georgia Tech’s Advanced Technology Development Center (ATDC) startup accelerator program and a GRA VentureLab company, Sub-Micro has also raised private funding to support its prototype development.

Challenges ahead include ensuring that nanoparticles cannot bypass the filtration system to enter the body, and controlling the risk of infection caused by opening the peritoneal cavity.

Beyond cancer, the researchers believe their approach could be useful for treating other diseases in which a reduction in circulating cancer cells or virus particles could be useful. Using magnetic nanoparticles engineered to capture HIV could help reduce viral content in the bloodstream, for instance.

“A technology like this has many different possibilities,” said Scarberry. “We are currently developing the technology to control the metastatic spread of ovarian cancer, but once we have a device that can efficiently and effectively isolate cancer cells from circulating fluids, including blood, we would have other opportunities.”

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Posted in Discoveries, Medical Study Results, Nanotechnology, Novel Therapies | Tagged: , , , , , , , , , , , , , , , , , , | Leave a Comment »

Georgia Tech’s Ovarian Cancer Early Detection Blood Test Exhibits High Accuracy in Small Study; Larger Study Planned

Posted by Paul Cacciatore on August 11, 2010

Scientists at the Georgia Institute of Technology have attained very promising results on their initial investigations of a new test for ovarian cancer. Using a new technique involving mass spectrometry of a single drop of blood serum, the test correctly identified women with ovarian cancer in 100 percent of the 94 patients tested. Because of the extremely low prevalence of ovarian cancer in the general population (∼0.04%), extensive prospective testing will be required to evaluate the test’s potential utility in general screening applications.

Scientists at the Georgia Institute of Technology have attained very promising results on their initial investigations of a new test for ovarian cancer. Using a new technique involving mass spectrometry of a single drop of blood serum, the test correctly identified women with ovarian cancer in 100 percent of the 94 patients tested. The results can be found online in the journal Cancer Epidemiology, Biomarkers, & Prevention Research.

John McDonald, Ph.D., Professor, Associate Dean for Biology Program Development, Georgia Institute of Technology; Chief Science Officer, Ovarian Cancer Institute

Facundo Fernandez, Ph.D., Associate Professor, School of Chemistry & Biochemistry, Georgia Institute of Technology

“Because ovarian cancer is a disease of relatively low prevalence, it’s essential that tests for it be extremely accurate. We believe we may have developed such a test,” said John McDonald, chief research scientist at the Ovarian Cancer Institute (Atlanta) and professor of biology at Georgia Tech.

The measurement step in the test, developed by the research group of Facundo Fernandez, associate professor in the School of Chemistry and Biochemistry at Tech, uses a single drop of blood serum, which is vaporized by hot helium plasma. As the molecules from the serum become electrically charged, a mass spectrometer is used to measure their relative abundance. The test looks at the small molecules involved in metabolism that are in the serum, known as metabolites. Machine learning techniques developed by Alex Gray, assistant professor in the College of Computing and the Center for the Study of Systems Biology, were then used to sort the sets of metabolites that were found in cancerous plasma from the ones found in healthy samples. Then, McDonald’s lab mapped the results between the metabolites found in both sets of tissue to discover the biological meaning of these metabolic changes.

The assay did extremely well in initial tests involving 94 subjects. In addition to being able to generate results using only a drop of blood serum, the test proved to be 100 percent accurate in distinguishing sera from women with ovarian cancer from normal controls. In addition it registered neither a single false positive nor a false negative

The group is currently in the midst of conducting the next set of assays, this time with 500 patients.

“The caveat is we don’t currently have 500 patients with the same type of ovarian cancer, so we’re going to look at other types of ovarian cancer,” said Fernandez. “It’s possible that there are also signatures for other cancers, not just ovarian, so we’re also going to be using the same approach to look at other types of cancers. We’ll be working with collaborators in Atlanta and elsewhere.”

In addition to having a relatively low prevalence, ovarian cancer is also asymptomatic in the early stages. Therefore, if further testing confirms the ability to accurately detect ovarian cancer by analyzing metabolites in the serum of women, doctors will be able detect the disease early and save many lives.

Libby’s H*O*P*E*™ Comment:

Alex Gray, Ph.D., Assistant Professor, College of Computing & Center for the Study of Systems Biology, Georgia Institute of Technology

This study involved testing the metabolite levels in blood sera from 44 women diagnosed with serous papillary ovarian cancer (stages I-IV) and 50 healthy women or women with benign conditions.  The assay distinguished between the cancer and control groups with an unprecedented 99% to 100% accuracy. The method possesses significant clinical potential as a cancer diagnostic tool.  Because of the extremely low prevalence of ovarian cancer in the general population (∼0.04%), extensive prospective testing will be required to evaluate the test’s potential utility in general screening applications.

Sources:

Initial Trials On New Ovarain Cancer Tests Exhibit Extremely High Accuracy, News Release, Georgia Institute of Technology, August 11, 2010.

Zhou M,Guan W, Walker LD, et. al. Rapid Mass Spectrometric Metabolic Profiling of Blood Sera Detects Ovarian Cancer with High Accuracy. Cancer Epidemiol Biomarkers Prev 1055-9965.EPI-10-0126; Published OnlineFirst August 10, 2010; doi:10.1158/1055-9965.EPI-10-0126

Posted in Biomarker, Early Detection, Medical Study Results | Tagged: , , , , , , , , , | 3 Comments »

Removal of Ovarian Cancer Cells From Human Ascites Fluid Using Magnetic Nanoparticles

Posted by Paul Cacciatore on February 1, 2010

Scientists at Georgia Tech and the Ovarian Cancer Institute have further developed a potential new treatment against cancer that uses magnetic nanoparticles to attach to ovarian cancer cells, removing them from the body. The treatment, tested in mice in 2008, has now been tested using samples from human ovarian cancer patients. The results appear online in the journal Nanomedicine.

Nanoparticles, in brown, attach themselves to ovarian cancer cells, in violet, from the human abdominal cavity. (Credit: Ken Scarberry/Georgia Tech)

Scientists at Georgia Institute of Technology (Georgia Tech) and the Ovarian Cancer Institute have further developed a potential new treatment against cancer that uses magnetic nanoparticles to attach to ovarian cancer cells, removing them from the body. The treatment, tested in mice in 2008, has now been tested using samples from human ovarian cancer patients. The results appear online in the journal Nanomedicine.

John McDonald Ph.D., Professor & Associate Dean for Biology Program Development, Georgia Institute of Technology; Chief Research Scientist, Ovarian Cancer Institute (Credit: Georgia Tech)

“We are primarily interested in developing an effective method to reduce the spread of ovarian cancer cells to other organs ,” said John McDonald, professor at the the School of Biology at the Georgia Institute of Technology and chief research scientist at the Ovarian Cancer Institute.

The idea came to the research team from the work of Ken Scarberry, then a Ph.D. student at Georgia Tech. Scarberry originally conceived of the idea as a means of extracting viruses and virally infected cells. At his advisor’s suggestion Scarberry began looking at how the system could work with cancer cells.

He published his first paper on the subject in the Journal of the American Chemical Society in July 2008. In that paper he and McDonald showed that by giving the cancer cells of the mice a fluorescent green tag and staining the magnetic nanoparticles red, they were able to apply a magnet and move the green cancer cells to the abdominal region.

Recently, McDonald and Scarberry (currently a postdoctoral fellow in McDonald’s lab) have shown that the magnetic technique works with human ovarian cancer cells.

Ken Scarberry Ph.D., Postdoctoral Fellow, McDonald Laboratory, Georgia Institute of Technology (Credit: Robert Felt, Georgia Tech.)

“Often, the lethality of cancers is not attributed to the original tumor but to the establishment of distant tumors by cancer cells that exfoliate from the primary tumor,” said Scarberry. “Circulating tumor cells can implant at distant sites and give rise to secondary tumors. Our technique is designed to filter the peritoneal fluid or blood and remove these free floating cancer cells, which should increase longevity by preventing the continued metastatic spread of the cancer.”

In tests, they showed that their technique worked as well with capturing ovarian cancer cells from human patient samples as it did previously in mice. The next step is to test how well the technique can increase survivorship in live animal models. If that goes well, they will then test it with humans.

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Posted in Discoveries, Nanotechnology, Preclinical Testing | Tagged: , , , , , , , | Leave a Comment »

 
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