A veterinary neurologist on faculty in the Virginia-Maryland Regional College of Veterinary Medicine(http://www.vetmed.vt.edu/) at Virginia Tech has been awarded funding from the Wake Forest University Translational Science Institute to study innovative approaches for treating brain tumors in dogs, cats and humans.

Dr. John Rossmeisl, an assistant professor in the Department of Small Animal Clinical Sciences (DSACS), is working with Wake Forest University Medical Center researchers to develop better therapeutic approaches for managing very serious forms of brain tumors called gliomas.

Rossmeisl will work closely with a cluster of scientists and physicians at Wake Forest University and with VMRCVM veterinary pathologist Dr. John Robertson, director of the college"s Center for Comparative Oncology, on the project. The veterinary college is a participating institution on a major translational research initiative at Wake Forest University funded by the National Institutes of Health (NIH).

"Gliomas are an aggressive and deadly form of brain cancer that affects dogs and people," said Rossmeisl, who is board certified in veterinary neurology by the American College of Veterinary Internal Medicine. "Because there are so many similarities between clinical signs and pathobiology, the dog has emerged as an excellent model for studying gliomas in humans."

Every year about 120,000 new cases of primary and secondary brain cancer are diagnosed, according to the National Cancer Institute. Much less is known about the incidence of brain tumors in domestic animals, according to Rossmeisl. Clinical signs associated with brain tumors in both people and animals can include seizures, abnormal behaviors, weakness of the limbs, loss of balance, blindness and other problems.

Gliomas arise from glial cells, according to Rossmeisl, which play numerous supporting roles for neurons, brain cells that control thought, sensations and motion. Glial cells outnumber neurons by a factor of about ten to one in the brain, and they play an essential role in creating the architecture and structure of the brain and supporting its functions.

There are several different specific types of glial cells, but two that interest Rossmeisl and colleagues most are called astrocytes and oligodendrocytes. Oncogenic abnormalities associated with each of these can lead to cancers called astrocytomas and oligodendrocytomas, according to Rossmeisl.

The most common approaches for managing these tumors involve surgical excision, radiation therapy and chemotherapy. But conventional radiation and chemotherapy affect normal cells in addition to the cancerous cells they target, so perfecting approaches that exclusively target the molecular abnormalities present in each individual"s cancer cells and spare healthy cells is a major thrust in modern oncology.

To develop more precisely targeted systems for administering therapeutic agents to cancer cells, Rossmeisl and his colleagues are attempting to further establish the molecular similarity of human and canine gliomas.

Scientists know that when astrocytomas spontaneously arise in people, they over-express three proteins: interleukin 13 receptor alpha2 (IL-13R), which is a cancer testis tumor like agent; EphA2, a tyrosine kinase receptor; and fos-related antigen 1, an AP-1 tranion factor.

Rossmeisl and colleagues working in the college"s Center for Comparative Oncology have opened a clinical trial and are currently enrolling animals from around the region that have been positively diagnosed with a brain mass consistent with the appearance of a glioma on magnetic resonance imaging (MRI).

The researchers will be studying tissue samples from affected animals in search of these proteins that are not otherwise present in normal brain tissues. Identifying these proteins could further document the dog"s suitability as a model for studying pre-clinical human disease, according to Rossmeisl, and ultimately lead to the development of more precisely targeted methods for managing these tumors.

Another portion of the work is focused on the development of powerful new cancer treatments. Through a process known as convection enhanced delivery (CED), the researchers are removing the diseased tissues and testing the application of a proprietary experimental compound. This agent is used to "bathe" the margins of the area in which the tumor was removed and it has been designed in a way that it will only bind with receptors in tumor cells expressing abnormal proteins.

"Their potential value is tremendous to humans and dogs with cancer," said Rossmeisl. These treatments may represent a significant advancement in prolonging survival in dogs and people with these highly aggressive cancers."

The researchers will also be looking at improved processes for performing radiation therapy on brain tumors in dogs.

"Currently, the standard of care in veterinary radiotherapy is fractional radiotherapy delivered with a linear accelerator," explained Rossmeisl. This form of radiation therapy is typically delivered with frequent administration of relatively small doses of radiation multiple days per week over several weeks. Though it can be fairly precisely targeted, it can affect tissues unrelated to the tumor.

The grant will enable the researchers to perfect protocols for treating canine patients with stereotactic radiosurgery - more commonly known as the "gamma knife." The gamma knife uses a specialized head-frame to target an exactingly focused beam of killing radiation with pin-point accuracy on the tumor itself. As opposed to a traditional course of radiotherapy that can take weeks, the gamma knife can accomplish the task in one session lasting a few hours.

 

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