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Early cancer treatment successes lead to CAREER Award for Rafael Davalos


   

Rafael Davalos Rafael Davalos of the Virginia Tech – Wake Forest School of Biomedical Engineering and Sciences has reported on early successful treatment of canine cancer in the Journal of Clinical Oncology, and has now received a National Science Foundation CAREER Award based on these successes.


BLACKSBURG, Va., April 11, 2011 – In a recent article in the Journal of Clinical Oncology, co-author Rafael Davalos described the use of a method he invented to successfully treat a seven-year-old spayed female Labrador retriever with a five-year history of degenerative coxofemoral joint disease. The dog’s frequent lameness led to the discovery of a mass that was consistent with a cancerous tumor. With traditional treatment, survival for such a patient is three to six months.

Davalos of the Virginia Tech–Wake Forest School of Biomedical Engineering and Sciences had five collaborators on the article: Robert E. Neal II and Paulo Garcia, also of the biomedical school, along with John H. Rossmeisl Jr., Otto I. Lanz, and Natalia Henao-Guerrero of the Virginia–Maryland Regional College of Veterinary Medicine, all at Virginia Tech.

They described how they used a combination of Davalos’ patent pending method of irreversible electroporation followed by the well-known medical treatment of chemotherapy to shrink the tumor. After the tumor developed resistance to the chemotherapy, they used irreversible electroporation a second time to completely eradicate all signs of the cancer. After six months, the authors reported in the Feb. 14, 2011 journal article that the family pet was in complete remission according to clinical and computerized tomography scans.

It is now 12 months since the team first treated the patient, and the dog remains in complete remission.

Today, the National Science Foundation has named Davalos as one of its 2011 recipients of a CAREER Award to continue his trailblazing research on the ability of irreversible electroporation to treat diseased cells with and without adjuvant chemotherapeutic agents or radiation. The CAREER award is the National Science Foundation’s most prestigious award in support of junior faculty who exemplify the role of teacher-scholars.

Davalos explained his novel process applies electrical pulses, each microseconds in length, to a targeted tissue area. The goal is to permanently open nanopores in the membranes of a cell, causing cell death. The destruction of the cells in this case is not due to injury from heat, and therefore doesn’t damage the supporting structures in the tissue, including the extracellular matrix, blood vessels, and nerves. “This accomplishment is very important since it allows the selective treatment of cells while respecting healthy tissue architecture,” Davalos added.

"The procedure is essentially done with two minimally invasive electrodes placed into the targeted region," Davalos said, "delivering approximately 80 pulses to the site in about one minute. The pulses are high voltage, but low energy, so no significant heating occurs as a result of the procedure."

With his CAREER award of $ 450,000, Davalos will specifically look at whether irreversible electroporation procedures can be adapted for the destruction of special tumors called glioblastoma multiforme, the most common and aggressive type of primary brain tumor in humans. The median survival for people diagnosed with these tumors is only 15 months. The team, which also includes Tom Ellis at Wake Forest University and John Robertson at the vet school, has already treated a canine patient with a brain tumor that was refractory to surgical resection. They used their procedure to kill a majority of the tumor volume, making it possible to treat the rest of the remaining cancer cells with radiation. At four months after treatment, there was no sign of the tumor.

“One of the reasons for the poor survival is that glioma cells typically infiltrate up to two centimeters beyond the volume of visible tumor,” Davalos explained. Since the electric field dissipates from the electrode, the process gives rise to regions of reversibly electroporated cells outside the ablation zone. These cells may then be more susceptible to the uptake of drugs.

“We propose to assess irreversible electroporation ‘s capacity to treat infiltrative cells within this reversible zone when combined with chemotherapeutic agents. Treatment of malignant gliomas is also limited by insufficient delivery of drugs due to the blood-brain-barrier. Therefore, this plan will also investigate whether [irreversible electroporation] can be applied to mediate blood-brain-barrier disruption to aid in the delivery of chemotherapeutic agents.,” Davalos said.

Davalos will use a combination of experiments and modeling on the molecular, cellular, and tissue levels. He says he believes that the broader impacts of his work will allow the medical community to use this therapy in other pathologies such as cardiac arrhythmias.

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