Illustration by Amy Charron

That’s why oncology research at Oregon State University’s College of Veterinary Medicine is attracting the attention of researchers at medical schools, including Oregon Health & Science University.

“Canine cancer often mimics human cancer,” says Stuart Helfand, who came to OSU in 2005 to begin the college’s oncology program. “But I’m a big believer in looking at cancer holistically; it’s not about humans on one side and dogs on another. It’s about studying and treating cancer. And there are ties between human and animal health, just as there is a bond between people and their pets.”

If OSU’s animal health clinic is the public face for the College of Veterinary Medicine, its research laboratories are the legs. Here is where Helfand and his colleagues study how cancer works in dogs and cats and what treatments may kill, or at least slow down, deadly cancer cells. Helfand’s interest in cancer research began in immunotherapy, which seeks to boost the immune system to fight cancer. Through this portal, his interests have expanded in a number of research directions.

Drs. Stuart Helfand, right, and Bernard Seguin are developing new cancer treatments in the OSU College of Veterinary Medicine. (Photo: Karl Maasdam)

“I was trained as a clinician but came to realize that there were many questions we could not answer in the clinic alone,” he says. “This attracted me to research in the laboratory with an eye toward learning things that could be brought back to our patients in the clinic, so-called translational research.”

A particularly aggressive form of cancer in dogs, known as hemangiosarcoma, drew Helfand’s attention because it has resisted attempts to find a cure. In cell cultures, it can be used to investigate angiogenesis, the process through which growing tumors develop a blood supply. Helfand is also studying proteins that act as chemical messengers, telling cells to reproduce and regulating other cellular activities. One type, an enzyme known as tyrosine kinase, serves as an “on” or “off” switch and also plays a role in human cancers.

“This field has expanded rapidly, and our laboratory is focused on learning how to exploit abnormal tyrosine kinases in several cancers that affect dogs and cats,” Helfand adds. “Through these efforts, we are hopeful we can improve care for animals while helping to establish these tumors as models for human cancer and contributing to improvements in human health.” Results from Helfand’s research have now begun to find their way into his clinical oncology practice.

Dogs are an attractive model for human cancers for two reasons: genetics and a shorter lifespan. People often live 75 years or more and may not develop cancer until late in life. Dogs, on the other hand, go through generations much more quickly and have distinct breeds with unique genetics, making them ideal for looking at the mechanisms leading to cancer. Why, for example, does bone cancer in humans affect teenagers at a disproportionate rate, and in dogs, primarily strike large breeds like Rottweilers, Saint Bernards, Irish wolfhounds and Great Danes?

A Surgeon’s Best Friend

Bernard Séguin, a small-animal surgeon with the college, discovered just how difficult it can be to have a pet stricken with cancer when his Rottweiler mix, George, developed bone cancer. He operated on the dog himself and helped extend his life several more months before the tumor made a fatal return. “Large-breed dogs are at great risk for bone cancers,” says Séguin, a native of Montreal who came to OSU from the University of California-Davis. “We aren’t quite sure why. Teenage humans also are at greater risk, and medical doctors want to know why. So we are working together.”

 

Saving Orion

Unlike humans, whose hair falls out during chemotherapy, dogs don’t lose their fur. I didn’t learn that when I was training to be an oncologist. I know it now because my dog has cancer.

Séguin is teaming with Dr. Charles Keller, an OHSU pediatric oncologist, on a joint study of bone cancer they hope will help both dogs and humans. And in the surgical suite, sometimes under extraordinary circumstances, Séguin is applying what Helfand and others are learning in the laboratory.

Last year, Holly, a greyhound, was referred to the OSU clinic with a tumor in her humerus bone. The tumor was in an unusual location, in the middle of the bone, rather than at the tip, which is much more common. The usual course of action for such tumors is to amputate the leg, because the surgery is so invasive and the tumor can spread. But as OSU researchers learn more about cancer, they are looking at other protocols.

In the first operation of its kind anywhere, Séguin and his colleagues removed the diaphysis, or the long shaft of the humerus, and replaced it with a section of Holly’s ulna, then performed microvascular surgery to connect tiny blood vessels, giving blood to the new bone structure instantaneously. “We are able to push the envelope here in part because we have the technological capability,” Séguin says. “We have the best CT scanner in veterinary medicine that allows us to do things we never dreamed of, and we have an operating microscope that few teaching hospitals have. We can match equipment with most vet colleges in the country.”

Regional Resource

Helfand has a vision of creating a regional cancer program at the college that would serve as a clinical resource for Northwest veterinarians, and that, as a leading research facility, would collaborate with medical researchers. What is missing, he says, is a building, endowed faculty positions and a linear accelerator for providing radiation treatment. Radiation therapy, he says, has both curative and palliative benefits for animals.

“When you remove a tumor surgically, the challenge is to get all the cancer tissue out,” Helfand says. “To be safe, you often remove some of the surrounding tissue. But soft tissue sarcomas frequently occur on the legs, where there isn’t a lot of soft tissue, which is why amputations frequently are the course of action. Radiation could help reduce amputations as well as reduce the animals’pain.

“It’s all about increasing the quality of life for the animals,” he adds.

When Helfand leaves the clinic floor en route to his research laboratory, he frequently walks by what he calls his “Wall of Heroes,” photos of animals treated for cancer at OSU. Most are dogs; some recovered from their disease, others did not. Each of them, he says, has a story.

“We had one dog, brought in by a gentleman who told us: ‘This is my son’s dog. My son just died, andthis is our last link to him. You must save him,’” Helfand explains. “That was emotional. In most cases, our lifespan exceeds that of our pets, and when you get a pet, you need to accept that you will experience heartbreak.

“Sometimes,” he adds, “it works out the other way.”

At the other end of the spectrum from heartache is hope, and the OSU oncology program is creating that for a growing number of visitors. Research advances, diagnostic and surgical skill and sophisticated technology are making the term “cancer” slightly less frightening.

Just ask Lucky. The 1-year-old golden retriever was training for hunting competitions when she developed a large aggressive tumor along her spine. It looked like her life would be cut short. In 2007, her owner, Rod Krahmer of Salem, brought Lucky to OSU where Helfand and Séguin collaborated on a treatment of chemotherapy and surgery.

“I am happy to report,” Krahmer wrote in a recent email to Helfand and Séguin, “that all is great four years post-op!!! There has been little effect from the surgery. She lost some range of motion when turning her head (neck) to the right, but compensates with no problems. Lucky has achieved her Master Hunter title and will be working towards an invitation to the Master National Hunt Test (the Super Bowl of retriever games) in Maryland this year!”

“That,” says Séguin, “is what we live for.

Ishan Patel developed a table-top model for testing blood coagulation. (Photo: Jan Sonnenmair)

It wasn’t the most elegant way to enter a lab. Ishan Patel had just met his mentor for the summer of 2009, Dr. Owen McCarty at Oregon Health & Science University. The OSU bioengineering student wanted to make a good impression, and when McCarty told him to go across the hall and meet his research team, Patel confidently tried the doors, only to trip the alarm just as a security guard and another person were leaving. “There was lots of confusion about who had set off the alarm,” Patel laughs.

Patel had walked into a facility shared by OHSU researchers studying optics, stem cells, neurology and blood chemistry. For the first-year student aiming for a career in medical research, it was a thrill just to be there. Once McCarty arrived and introduced Patel to the other members of his team, Patel received his marching orders: build a table-top device that would allow liquid to flow under the force of gravity from a reservoir through a capillary tube into a reservoir.

Patel recalls his exact words. “He said, ‘I don’t know how you’re going to do this. Here’s a catalog book to find parts. If you need anything, you can order what you want. Just get it done.’” The device would provide a model for McCarty’s studies of blood clot formation.

After three weeks and several attempts, which involved burning small holes in plastic Petri dishes and applying glue to silicon tubing, Patel was testing a prototype when McCarty came into the lab. “He saw it and said ‘that looks good. Let’s add some blood.’ So we pipetted some blood through a syringe, and it flowed right through into the capillary and into the bath. No leaks, nothing.”

That was the first success for Patel who is also a student in OSU’s University Honors College. Since then he has worked on a mathematical model of blood flow in the device to make sure it is physiologically relevant to human arteries and veins. In 2010, he returned to McCarty’s lab to study the influence of cancer cells on blood coagulation. He is listed as a co-author on four peer-reviewed papers on blood chemistry and coagulation.

Patel credits OSU engineering professor Willie “Skip” Rochefort with encouraging him and helping him to earn a Pete and Rosalie Johnson Scholarship during his internship at OHSU. “When I came to OSU, I really wanted to start doing research,” says Patel. “I came from a small town, Redmond, Oregon, and I never expected to be able to get into a research lab right away and start producing results that quickly.

“The fact that I get to spend my four years with the same people, that I develop relationships with my peers and professors — that provides a really good education environment.”

Patel advises fellow students considering research to be persistent and be open to opportunities. “Try anything and everything you want,” he adds. “Keep your goals in mind. If you want to go on to grad school, avoid getting sidetracked by distractions.”

This spring, Patel learned that he had received a Goldwater Scholarship, one of the nation’s most prestigious awards for undergraduate researchers. In July, he plans to present a paper to the International Society of Thrombosis and Haemostasis in Kyoto, Japan.