Research Breakthrough

Tumor remission experiments at Reidy Center prove promising

By Jim Raper

Pulses of electricity shorter than a millionth of a second can cause complete remission of melanomas on the skin of mice, researchers at the Frank Reidy Research Center for Bioelectrics reported in a paper published online March 10 in Biochemical and Biophysical Research Communications.

Previous experiments at the Reidy Center, which is operated by Old Dominion and Eastern Virginia Medical School, had shown that nanosecond-range pulses of relatively high field strength could reduce tumor size and mass by cell “suicide.” The latest results extend these earlier studies showing that the process – with field strengths ranging as high as 40,000 volts/cm – can cause skin tumors to self-destruct.

Following this treatment, tumor cell nuclei shrink by 50 percent within minutes and the tumor blood supply is disrupted for weeks. The paper also suggests that tumors inside the body may respond to a similar treatment delivered by catheter electrodes.

Richard Nuccitelli, a biophysicist on the ODU faculty and a researcher at the Reidy Center, believes the results are an important step toward human cancer treatments that involve no drugs and produce no lasting side effects. The paper notes that the pulsed electric field also seems capable of curing skin cancers without causing the scarring left by surgical incisions.

“We see these results as very important,” said Nuccitelli, first author of the paper. “We want to continue the research to learn more about how the pulses work.”

Another of the paper’s authors, Karl H. Schoenbach, is director of the Reidy Center and a leading expert in the new field of intracellular electromanipulation. An eminent scholar of electrical and computer engineering, Schoenbach also is Batten Endowed Chair in Bioelectrics Engineering at Old Dominion.

Earlier papers from Schoenbach’s research group have described pulsed electric field experiments that destroyed cancer cells through apoptosis – an orderly self-destruct mechanism.

The nanosecond-range electric field pulses produce remarkable effects compared to longer pulses because of the field’s penetration of the outer cellular membrane. Membranes typically resist penetration by electric fields, but the ultrashort pulses, lasting only 300 nanoseconds or 0.3 millionths of a second each, essentially sneak through before the outer membrane can mount a defense. Once inside the cell, the electric field is able to act upon the nucleus and other intercellular organelles.

Soon after the pulsed electric field penetrates tumor cells, the nuclei shrink – possibly because of DNA damage – and blood supply to the melanoma is cut off, according to the researchers. In a study that lasted more than a year involving the treatment of 300 tumors on 120 mice, the researchers consistently were able to shrink melanomas by 90 percent within two weeks of initial treatment. Pulse applications to the tumors varied in length and staging, but generally comprised a series of pulses with a total duration much shorter than the blink of an eye. The researchers reported that after two weeks, melanomas began to regenerate, requiring a second treatment before complete remission was accomplished.

Because of the short duration, the pulses cause no significant heating of the tumor; researchers also observed no lasting damage to healthy cells surrounding the tumor.

Schoenbach predicts that cell electromanipulation “will end up in your doctor’s office” with applications not only for tumor treatment, but also for gene therapy, wound healing, removal of warts, treatment of fungal infections and other cosmetic uses. “The effects that have been observed so far are only the tip of the iceberg,” he said.

Researchers at the Reidy Center are now conducting experiments to determine if a mouse can survive a melanoma and still be healthy four to six months after treatment, as well as planning further research to explain how it is that nanosecond pulsed electric fields impact both diseased and healthy cells. Nuccitelli said experiments on higher mammals may be required before the researchers turn to human subjects.

The work reported in the paper was supported by grants from the Air Force Office of Scientific Research, American Cancer Society, ODU Educational Foundation, BioElectroMed Corp., a gift from Frank Reidy and with internal funds of the Reidy Center.