Tag Archives: cancer

Estrogen’s opposing effects on mammary tumors in dogs

Dogs that are spayed at a young age have a reduced risk of developing mammary tumors, the canine equivalent of breast cancer. Early spaying reduces levels of estrogen production, leading many veterinarians and scientists to cast estrogen in a negative light when it comes to mammary cancer.

But the effects of estrogen on cancer risk in dogs aren’t straightforward, according to a new study led by researchers from Penn’s School of Veterinary Medicine. While it’s clear that spaying dogs greatly minimizes their risk of developing mammary cancer, the findings suggest that the practice may increase the risk of more aggressive cancers. And in spayed animals with mammary tumors, the team found that higher serum estrogen levels were actually protective, associated with longer times to metastasis and improved survival times.

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Veterinary oncologist Karin Sorenmo and colleagues cast new light on the complex role of estrogen in canine mammary cancer. The research emerged from Penn Vet’s Shelter Canine Mammary Tumor Program, which assists in treating and then finding homes for dogs like Brownie, pictured with former oncology intern, Kiley Daube.

“Dogs that remain intact and have their ovaries develop many more mammary tumors than dogs that were spayed, so removing that source of estrogen does have a protective effect,” says Karin U. Sorenmo, a veterinary oncologist at Penn Vet and senior author on the study, published in PLOS ONE. “Estrogen does seem to drive mammary cancer development. But what it does for progression to metastasis—that I think is more complicated.”

Sorenmo and colleagues have been studying mammary tumors in dogs as a way of improving care and treatment for pets but also to make insights into human breast cancer biology.

“Much of the research we do in veterinary medicine looks at what is done in people and then adapts it,” she says. “But dogs are such a great, comprehensive model for cancer. Yes, there are differences in biology between dogs and people, but here those differences may allow us to ask very probing questions about what estrogen is doing in both dogs with mammary cancer and women with breast cancer.”

The research used data from two prospective studies, including one involving dogs in the Penn Vet Shelter Canine Mammary Tumor Program, through which shelter dogs with mammary tumors receive treatment, are studied by researchers like Sorenmo, and then find foster or permanent homes.

The team evaluated 159 dogs with mammary cancer, 130 that were spayed as part of the study and 29 that remain intact. In addition to surgically removing the dogs’ measurable tumors, the team collected information on serum estrogen levels, tumor type, disease grade and stage, time to metastasis, and survival time.

Despite estrogen’s link with an increased risk of developing mammary tumors, the researchers found that higher serum estrogen levels also seemed to help dogs avoid some of the riskiest aspects of their disease. Unexpectedly, when dogs were spayed at the same time their tumors were removed, those with estrogen receptor-positive tumors that had higher serum estrogen took longer to develop metastatic disease and survived longer than dogs with lower estrogen levels, confirming that these tumors depended on estrogen for progression.

Sorenmo speculates that, in these cases, estrogen’s action may be nuanced. “It drives the cancer, but it also seems to control or modulate it, reining it in,” she says, because most dogs with high serum estrogen levels had lower-grade and estrogen receptor-positive tumors, rendering them susceptible to hormonal deprivation by spaying.

The protective role of estrogen was also surprisingly pronounced in dogs with estrogen-receptor negative mammary tumors. In these higher-risk cancers, high serum estrogen was associated with delayed or absent metastasis. Complementing these findings and supporting a potential broader, tumor receptor-independent anti-cancer effect driven by estrogen, dogs with low serum estrogen had a significantly increased risk for developing other non-mammary aggressive fatal tumors, such as hemangiosarcoma, during their follow-up after mammary tumor surgery.

Some of the findings contradict what has been found in women with breast cancer. For example, higher serum estrogen levels in women following breast cancer therapy have been associated with higher rates of recurrence. But Sorenmo also notes that many cases of breast cancer in women arise just after menopause, when estrogen levels tumble. So there may be a more complex role for estrogen in people’s cancer risk as well.

The work points to new possibilities for examining the role of estrogen in cancer initiation and progression. Already, Sorenmo and colleagues, including Penn Vet’s Susan Volk and Ellen Puré, are pursuing investigations of how the hormone affects the tumor microenvironment, cells that aren’t themselves cancerous but may either stem or encourage a tumor’s growth and spread.

“I think this study opens some really complicated questions,” Sorenmo says. “If we start dissecting exactly what estrogen is doing, what genes or immune cells it’s interacting with, maybe we could harness the power of estrogen to be more clever in our treatment strategies.”

Source:  Penn Today

Muscle loss and wasting

I encounter dogs in my practice who are experiencing muscle loss and wasting fairly often.

Since owners must submit veterinary records to me for review as part of my intake process as well as update me on any subsequent vet visits, if there’s a diagnosis of chronic illness – such as kidney disease or cancer – then this muscle loss  is understandable and classified as cachexia.

In the absence of a diagnosis of disease, and working with an aging dog, then the muscle loss is classified as sarcopenia.

Muscle loss results in a change of appearance, which owners often notice first around the shoulder blades, top of the head, and around the pelvis.  Muscle wastage can be graded as noted below:

Muscle condition score

Exercise and good nutrition can be interventions with muscle loss.  Chronically ill dogs need a high quality diet that is appropriate for their disease, for example.  And aging dogs do need exercise that is targeted to their needs and abilities.

Owners should always be on the watch for signs of muscle loss – so early interventions that are medical and non-medical can be considered.

Kathleen Crisley, Fear-Free certified professional and specialist in dog massage, rehabilitation and nutrition/food therapy, The Balanced Dog, Christchurch, New Zealand

Willa – Our Sweet Girl

Willa is a special dog.

An American Pit Bull x Boxer, Willa has breast cancer which has likely spread. She’s on medication, but with time being precious, it’s important to focus on quality of life.   Willa is a popular sleepover dog at Best Friends Animal Sanctuary – every precious sleepover adds to Willa’s quality of life and enrichment.  She really enjoys getting out of kennels, getting cuddles and having a good, deep sleep.

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Willa loves rides in the car

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A special tag for a special girl

I really enjoyed staying with Willa and seeing her sweet nature in person.  Let’s hope she gets a home soon.

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

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

Dogs help in breast cancer research

Cancer is one of the most frequent diseases not only in people, but in pets as well. Like people, dogs can also suffer from cancer of the mammary glands (mammary tumors). Dog mammary tumors are very similar to breast carcinoma in humans, and much more so than those of rats or mice, for example. For this reason, research on canine mammary tumors is important for human medicine as well. A study performed at the University of Zurich has now shown how similar mammary tumors are in both people and dogs.

Enni Markkanen, Vetsuisse-Fakultät Zürich, Untersuch Hund

Cancerous cells reprogram healthy cells

For the development of tumors and the progression of a carcinoma, not only the characteristics of the cancer cells themselves are decisive, but also the cells surrounding the tumor play a major role in this. Many tumors even have the capability to reprogram healthy cells in the tumor environment in a way that they start to support the growth of the cancerous cells. This mechanism plays an essential role in human breast carcinoma – but is it the same for dogs? The similarity of breast carcinoma in dogs and humans has been known for a long time. “But whether these tumor cells also influence the surrounding tissue in dogs the same way they do in humans was unknown until now”, explains Enni Markkanen of the Institute of Pharmacology and Toxicology of the Vetsuisse Faculty of the University of Zurich.

Archived tissues are of great value to the research

The researchers analyzed the surrounding tissue of canine mammary tumors using molecular biology and immunohistological methods. To do this, they could access the tissue archive of the Institute of Veterinary Pathology located at the Animal Hospital. “With the permission of our patient’s owners, we conduct pathological tests to better understand diseases,” says animal pathologist Alexandra Malbon. “In the process, we archive samples of various organs and tissues as these samples can be of great value to answer future research questions.”

Dogs suffering from cancer aid cancer research for humans

In the archived samples of mammary tumors from dog patients, Enni Markkanen and her team were able to prove that some cells in the vicinity of tumors behave the same way as the corresponding cells in humans: In the healthy tissue surrounding the tumor, substances are produced that promote tumor growth. “Simply speaking, the tumor enslaves its environment: It forces the surrounding cells to work for its benefit,” Markkanen adds. This mechanism works the same in both humans and dogs. For research on breast carcinoma, tumor tissue of dogs is therefore, among other reasons, much better suitable than tissue from rats or cells cultivated in the laboratory. “Importantly, however, we don’t view our dog patients as test subjects for cancer research,” Markkanen says. “But they can help us to better understand breast carcinoma in both dogs and humans and fight it more effectively.”

Source:  University of Zurich media statement

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.

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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

The history of canine transmissible venereal cancer

Researchers at the University of Cambridge have produced this interesting YouTube video about how canine transmissible venereal cancer has spread over time.  If you are interested in evolution, genetics or DNA research – this video is for you.

See also my previous posts:

A dog cancer that is 11,000 years old

Global snapshot of infectious canine cancer

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