Tag Archives: osteosarcoma

Elevated cholesterol’s link with canine osteosarcoma includes a better prognosis

Note from Doggy Mom:  I follow lots of areas of research in the canine field, but anything to do with osteosarcoma is interesting to me since greyhounds are known for suffering from this type of cancer.  Izzy is a greyhound!


Usually thought of as a health detriment, elevated cholesterol may play a role in longer survival times for dogs with a common form of bone cancer.

In addition to their veterinary significance, the findings by Oregon State University researchers advance the understanding of a type of malignant tumor, osteosarcoma, that’s often diagnosed in humans as well, typically afflicting teenagers and young adults.

Dog with cancer

A dog with osteosarcoma; Photo courtesy of Oregon State University

“This is one of the first steps into identifying cholesterol as a potential biomarker for canine osteosarcoma,” said Haley Leeper, a veterinary oncology resident at the OSU College of Veterinary Medicine. “We don’t have answers as to why high cholesterol is associated with this disease and with a better prognosis, but we’re hoping to advance these findings in future research.”

Leeper and collaborators at OSU and Iowa State University compared 64 dogs with osteosarcoma against two control groups: 30 dogs that had suffered traumatic bone fractures and 31 healthy dogs similar in age and weight to the animals with cancer.

Researchers found nearly half of the dogs with cancer – 29 of the 64 – had elevated levels of total serum cholesterol, a dramatically higher rate than occurred in either control population; just three of the 30 dogs with broken bones, and only two of the 31 healthy animals, showed high cholesterol.

Of the dogs stricken with osteosarcoma, 35 had the cancer in a leg which was subsequently amputated, followed by chemotherapy, which is the standard-of-care treatment; the dogs with elevated total cholesterol had a median survival time of 455 days, more than 200 days greater than the median survival time  for dogs with normal cholesterol.

“When people think of cholesterol they think of cheeseburgers and heart attacks,” Leeper said. “However, cholesterol is involved with many key processes and structures in the body like cell membranes, bone health and the immune system.”

Future studies that follow dogs long term and look at specific lipid content in the blood may shed light on the mechanisms behind cholesterol’s role in enhanced survival, Leeper said.

“There are a lot of things we plan on investigating,” she said. “This is exciting and fascinating, partly due to the comparative medical aspects between human research and our research.”

Source:  Oregon State University media release

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Scientists test nanoparticle drug delivery in dogs with osteosarcoma

At the University of Illinois, an engineer teamed up with a veterinarian to test a bone cancer drug delivery system in animals bigger than the standard animal model, the mouse. They chose dogs – mammals closer in size and biology to humans – with naturally occurring bone cancers, which also are a lot like human bone tumors.

wikimedia-commons-photo-of-bmd

Dogs with naturally occurring cancers are more similar in size and biology to humans than are other mammals, such as mice. Public domain photo: Wikimedia Commons

In clinical trials, the dogs tolerated the highest planned doses of cancer-drug-laden nanoparticles with no signs of toxicity. As in mice, the particles homed in on tumor sites, thanks to a coating of the drug pamidronate, which preferentially binds to degraded sites in bone. The nanoparticles also showed anti-cancer activity in mice and dogs.

The researchers report their results in the Proceedings of the National Academy of Sciences.

These findings are a proof-of-concept that nanoparticles can be used to target bone cancers in large mammals, the researchers said. The approach may one day be used to treat metastatic skeletal cancers, they said.

The dogs were companion animals with bone cancer that were submitted for the research trials by their owners, said U. of I.  Professor Dr Timothy Fan, who led the study with materials science and engineering Professor Jianjun Cheng.  All of the dogs were 40 to 60 kilograms (88 to 132 pounds) in weight, he said.

“We wanted to see if we could evaluate these drug-delivery strategies, not only in a mouse model, but also at a scale that would mimic what a person would get,” Fan said. “The amount of nanoparticle that we ended up giving to these dogs was a thousand-fold greater in quantity than what we would typically give a mouse.”

Using nanoparticles with payloads of drugs to target specific tissues in the body is nothing new, Cheng said. Countless studies test such approaches in mice, and dozens of “nanopharmaceuticals” are approved for use in humans. But the drug-development pipeline is long, and the leap from mouse models to humans is problematic, he said.

“Human bone tumors are much bigger than those of mice,” Cheng said. “Nanoparticles must penetrate more deeply into larger tumors to be effective. That is why we must find animal models that are closer in scale to those of humans.”

Mice used in cancer research have other limitations. Researchers usually inject human or other tumor cells into their bodies to mimic human cancers, Fan said. They also are bred to have compromised immune systems, to prevent them from rejecting the tumors.

“That is one of the very clear drawbacks of using a mouse model,” Fan said. “it doesn’t recapitulate the normal immune system that we deal with every day in the person or in a dog.”

There also are limitations to working with dogs, he said. Dogs diagnosed with bone cancer often arrive at the clinic at a very advanced stage of the disease, whereas in humans, bone cancer is usually detected early because people complain about the pain and have it investigated.

“On the flip side of that, I would say that if you are able to demonstrate anti-cancer activity in a dog with very advanced disease, then it would be likely that you would have equivalent or better activity in people with a less advanced stage of the disease,” Fan said.

Many more years of work remain before this or a similar drug-delivery system can be tested in humans with inoperable bone cancer, the researchers said.

Source:  Illinois News Bureau media release

Kathleen Crisley, specialist in dog massage, rehabilitation and nutrition/food therapy, The Balanced Dog, Christchurch, New Zealand

Clinical trials to help beat cancer

Raelene Wouda’s passion for improving cancer treatment starts with our four-legged friends.

Dog cancer photo
Wouda, Kansas State University assistant professor of clinical sciences, is conducting clinical trials to treat cancers in dogs, cats and other companion animals.

When pet owners bring their dogs, cats, horses and other animals to the College of Veterinary Medicine’s Veterinary Health Center for treatment, Wouda and the Oncology Service can offer groundbreaking new treatments often at a lower cost to pet owners.

Wouda also is able to study important topics, such as improved diagnostic testing, monitoring approaches and innovative treatment options, including anti-cancer vaccines, t-cell transfer, combination chemotherapy and nanoparticle drug formulations. She has recently published her research in Veterinary Comparative Oncology and the Journal of the American Veterinary Medical Association.

“Although surgery, radiation therapy, chemotherapy and, more recently, immunotherapy have improved patient outcomes, many cancers still do not have a long-term cure,” said Wouda, a clinical veterinary oncologist. “These clinical trials are a crucial step.”

But Wouda’s research benefits humans, too. Many cancers in animals — especially dogs — are similar to those in humans, which means that the diagnosis, monitoring, treatment and response to treatment are also similar.

“Any research that we do in our patients has the potential to provide important information for how the disease can be better diagnosed, monitored and treated in human patients,” Wouda said. “That’s what I would like to do with our research. I would like to continue to improve outcomes for our veterinary patients and, by extension, help human cancer patients.”

Companion animals offer several research advantages. Wouda’s clinical trial program focuses primarily on dogs because of the similarities between their cancers and human cancers, such as osteosarcoma, melanoma, lung cancer and urogenital cancers. Osteosarcoma, for example, is both clinically and genetically almost identical in dogs and human pediatric patients.

Dogs also live with us and are exposed to the same environmental factors. Additionally, because dogs age faster than humans — one dog year is equivalent to seven human years — their diseases progress faster, which is a practical advantage for rapidly evaluating a new treatment’s efficacy and clinical benefit, Wouda said.

“We get clinical answers more quickly in dogs,” Wouda said. “The benefit of a particular therapy becomes evident in dogs more rapidly compared to people, and because of this we can preserve research and development finances, but more importantly, we save valuable time and resources.”

Animal clinical trials are structured similarly to human clinical trials and are tightly regulated and overseen. Wouda works with Mary Lynn Higginbotham, associate professor of clinical sciences, their graduate students and oncology technicians as well as the Veterinary Health Center’s referring veterinarians to conduct these clinical trials. They also collaborate with human medical researchers to discuss how the research can best be applied in the field of human oncology.

“For many pet owners, cancer is a terminal diagnosis for their beloved family member,” Wouda said. “These studies provide owners an opportunity to trial a cutting-edge therapy for their pets at a reasonable price. Moreover, owners participating in these clinical trials take comfort and are pleased to know that they are helping to achieve better treatments and outcomes for pets that may be diagnosed with cancer in the future.”

Source:  Kansas State University

Drug trials in pet dogs with cancer

Physiological similarities between dogs and humans, and conserved genetics between some dog and human cancers, can allow pet dogs to serve as useful models for studying new cancer drugs, says Dr Timothy Fan of the University of Illinois.

Timothy Fan, professor of veterinary clinical medicine. With his personal dog, Ember

Timothy Fan, professor of veterinary clinical medicine. With his personal dog, Ember  photo by L. Brian Stauffer

In a meeting sponsored by the National Cancer Policy Forum of the National Academies’ Institute of Medicine in Washington, D.C., Fan and 15 other experts in the field described the benefits of using pet dogs with naturally occurring (rather than laboratory-induced) tumors in early cancer drug trials.

“We have a lot of dogs in the United States, approximately 70 million of them, and it’s believed that about 25 percent of pet dogs will develop some form of cancer in their lifetime,” he said. “We’re using dogs to help guide drug development for people, but at the same time we’re offering new, innovative therapies that would otherwise never be available to dogs, to help them as well.”

Several attributes make pet dogs attractive subjects for such studies, Fan said.

“Dogs tend to develop cancer as a geriatric population, just like people,” he said. “Because the tumors develop spontaneously, there is heterogeneity in that tumor population, as a human being would have. The size of the tumors and the speed of growth of those tumors are comparable in dogs and human beings. So there are many attributes of a dog that develops cancer spontaneously that recapitulate the biology that we see in people.”

Some studies have already begun using dogs to test new cancer therapies. Starting in 2007, for example, Fan began testing an anti-cancer drug called PAC-1  in pet dogs with naturally occurring lymphomas and osteosarcomas. The results in dogs allowed the scientists to advance PAC-1 as a potential therapy against human cancers. The drug is now in phase I human clinic trials.

“Another example in which dogs have been important in demonstrating drug activity was an anti-cancer compound produced by the pharmaceutical company Gilead Sciences,” he said. “The company produced a pro-drug, which must be activated by a naturally occurring enzyme in human leukocytes before it can become effective. Mice and rats lack this enzyme, but dogs have it, so the compound was tested in dogs.”

There also are limitations to the use of pet dogs in cancer drug trials.

“There are some tumors that will not be that relevant,” Fan said. “Colon cancer, for example, is heavily driven by diet, and we don’t see much colon cancer in dogs. So pet dogs might not be a suitable model for colon cancer in humans.”

“There is heterogeneity in the human population and in dogs. So I would argue that if your drug agent produces positive results in dogs, that would give me greater confidence that those findings would be translatable to people.”

Source:  University of Illinois media release

A biological trigger for canine bone cancer?

Researchers at the University of Wisconsin-Madison School of Veterinary Medicine have identified the biological mechanism that may give some cancer cells the ability to form tumors in dogs.

Yurtie, a canine cancer patient, in the UW Veterinary Care oncology ward.  Photo: Nik Hawkins

Yurtie, a canine cancer patient, in the UW Veterinary Care oncology ward.
Photo: Nik Hawkins

The recent study uncovered an association between the increased expression of a particular gene in tumor cells and more aggressive behavior in a form of canine bone cancer. It may also have implications for human cancers by detailing a new pathway for tumor formation.

The findings of the research have been published  in the journal Veterinary and Comparative Oncology and may eventually provide oncologists with another target for therapy and improve outcomes for canine patients with the disease.

The researchers examined cell lines generated from dogs with osteosarcoma, a common bone cancer that also affects people, with the intent of uncovering why only some cells generate tumors. After the dogs underwent tumor-removal surgery, cells from the tumors were grown in the lab.

This led to six different cancer cell lines, which were then transplanted into mice. The researchers then looked to see which lines developed tumors and which did not and studied the differences between them.

“We found several hundred genes that expressed differently between the tumor-forming and nontumor-forming cell lines,” said Timothy Stein, an assistant professor of oncology. However, one protein called frizzled-6 was present at levels eight times higher in cells that formed tumors.

“It’s exciting because it’s kind of uncharted territory,” says Stein “While we need more research to know for sure, it’s possible that frizzled-6 expression may be inhibiting a particular signaling pathway and contributing to the formation of tumor-initiating cells.”

The team’s genetic research will continue on dogs and be extended to humans.

Source:  University of Wisconsin-Madison media release

A vaccine for canine osteosarcoma?

Osteosarcoma is a highly aggressive bone tumor that affects at least 10,000 dogs annually in the United States, alone.

Photo by osteosarcomaindogs.org

Photo by osteosarcomaindogs.org

It is estimated that 90-95 percent of canine osteosarcoma subjects have microscopic metastatic disease (spread of cancer cells to other parts of the body at the time of diagnosis). Standard of care includes removal of the primary tumor—usually by amputation—followed by chemotherapy. Systemic chemotherapy given after amputation delays the development of metastatic disease; however, despite treatment, most dogs die of the disease within one year of diagnosis.

A new option may be available in the future if Dr. Nicola Mason’s research at the University of Pennsylvania School of Veterinary Medicine produces satisfactory results. Mason, an assistant professor of medicine and a Board-certified ACVIM Diplomate in Small Animal Internal Medicine, is evaluating the first vaccine for canine osteosarcoma.

The approach harnesses the power of the dog’s immune system, “training” it to seek out and destroy cancer cells that remain after amputation and chemotherapy.

Over a century ago, an orthopedic surgeon named William Coley recognized that human sarcoma patients with concurrent bacterial infections that caused high fevers had improved overall survival times compared to those sarcoma patients without infection. This led him to develop a therapeutic concoction of live bacteria that he injected into patients with bone sarcomas. He documented improved survival and in some cases, complete remission in individuals with the aggressive disease by using this early form of “immune therapy.”

Mason’s team is employing similar immune therapeutic strategy to treat dogs with osteosarcoma that have undergone the standard of care treatment (amputation and chemotherapy) to prevent metastatic disease. “The concept is that administration of the Listeria-based (genetically modified bacteria) vaccine will activate the patient’s immune system and educate it to recognize cells that express the target molecule,” says Mason.

Dogs are given the live bacterial vaccine intravenously, Mason explains, and it induces a mild transient fever on the day of vaccination. The dogs are usually treated as outpatients and return home the same day. “We have found highly encouraging results when the vaccine is given to patients that have no evidence of metastatic disease at the time of the study enrollment, which is three weeks after the last chemotherapy is administered. Four out of the first five dogs vaccinated are alive at least two years after their initial diagnosis, which is more than twice their expected survival duration. The vaccine has not yet shown any serious short- or long-term side effects, either.”

Mason says the results have led researchers to evaluate whether this vaccine may be able to directly target and kill the bone tumor itself, perhaps eliminating the need for amputation in the future.

Source:  American College of Veterinary Internal Medicine media release