Tag Archives: cancer cells

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

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Immunotherapy hope

There is a form of cancer treatment called immunotherapy, where antibodies inhibit tumor growth.  Until now, such therapy wasn’t available for dogs.  A research team at Messerli Research Institute of the Vetmeduni Vienna, the Medical University of Vienna and the University of Vienna have now developed antibodies to treat cancer in dogs.

The newly developed antibody brings hope for dogs. (Photo by:  Michael Bernkopf / Vetmeduni Vienna)

The newly developed antibody brings hope for dogs. (Photo by: Michael Bernkopf / Vetmeduni Vienna)

Since cancer cells bear very specific antigens on the surface, the corresponding antibodies bind to these molecules and inhibit tumor growth.  A destructive signal sent by the antibody to the inside of the cancer cell initiates its death. In a second mechanism, the immune system of the patient also destroys the “marked” tumor in a more efficient way.

Josef Singer and Judith Fazekas, both lead authors of the study, discovered that a receptor frequently found on human tumor cells (epidermal growth factor receptor or EGFR) is nearly 100 percent identical with the EGF receptor in dogs. In human medicine EGFR is frequently used as the target of cancer immunotherapy because many cancer cells bear this receptor on their surface. The so-called anti-EGFR antibody binds to cancer cells and thus triggers the destruction of the cells. “Due to the high similarity of the receptor in humans and dogs, this type of therapy should work well in dogs too,” the scientists say. The binding site of the antibody to EGFR in man and dogs differs only in respect of four amino acids.

The head of the study, Professor Erika Jensen-Jarolim, explains as follows: “We expect dogs to tolerate these anti-cancer antibodies well. This will be investigated in clinical studies in the future and is expected to greatly improve the treatment as well as the diagnosis of cancer in dogs.”

The newly developed antibody provides an additional benefit for dogs. As in human medicine, antibodies can be coupled with signal molecules. When the antibody binds to a cancer cell in the organism, the coupled antibody – in this case a radioactive isotope – can be rendered visible and is thus able to show where tumors and even metastases are located. When the selected isotope also contributes to the decay of cancer cells, the approach is known as “theranostics” (therapy and diagnostics).

In veterinary medicine, immunotherapy will be employed for the treatment of mammary ridge cancer (milk line cancer) in dogs. It may also be used as part of a combination therapy.

The team have published their study results in the journal Molecular Cancer Therapeutics.

Source: Vetmeduni Vienna 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

A dog cancer that is 11,000 years old

Scientists have sequenced the genome of the world’s oldest continuously surviving cancer, a transmissible genital cancer that affects dogs.

Credit: © Melinda Nagy / Fotolia

Credit: © Melinda Nagy / Fotolia

The cancer, which causes grotesque genital tumours in dogs around the world, first arose in a single dog that lived about 11,000 years ago. The cancer survived after the death of this dog by the transfer of its cancer cells to other dogs during mating.

Analysis of the genetic variants in the genome revealed that the dog may have resembled an Alaskan Malamute or Husky. It probably had a short, straight coat that was coloured either grey/brown or black. Its genetic sequence could not determine if this dog was a male or a female, but did indicate that it was a relatively inbred individual.

The genome has over 2 million mutations; the research team used one type of mutation, known to accumulate steadily over time, as a ‘molecular clock.’  This led to the estimate that the cancer first arose 11,000 years ago.

“The genome of this remarkable long-lived cancer has demonstrated that, given the right conditions, cancers can continue to survive for more than 10,000 years despite the accumulation of millions of mutations”, says Dr Elizabeth Murchison, first author from the Wellcome Trust Sanger Institute and the University of Cambridge.

Transmissible cancers are very rare in nature.  Apart from the dog transmissible cancer, the only other known naturally occurring transmissible cancer is an aggressive transmissible facial cancer in Tasmanian devils that is spread by biting.

Source:  Wellcome Trust media statement