2018 research HIGHLIGHTS
Biomarker May Provide Early Cancer Detection
With A Simple Blood Test, Dogs With Osteosarcoma Could Begin Treatment Before Cancer Spreads
Canine osteosarcoma is the most commonly diagnosed bone cancer, and is often very aggressive in spreading to the lungs and other areas. Once the tumor metastasizes, dogs only live, on average, a couple of months, even with chemotherapy.
The best case scenario for saving a pet with osteosarcoma is to catch it early, before it spreads, and remove the tumor. This can add years to a dog’s life. The current method of diagnosing canine osteosarcoma is done with a CT scan, followed by a biopsy to determine if the tumor is benign or malignant, a procedure that is invasive and costly.
Dr. Shay Bracha, a canine oncologist at the OSU Veterinary Teaching Hospital (VTH), is working on a less invasive, more effective screening for osteosarcoma.
Cancer spreads by compromising the immune system. Dr. Bracha’s research team has been investigating the role of exosomes in immunosuppression. Exosomes are tiny structures made in the body’s cells that are thought to be involved in signaling between cells.
The Bracha team exposed healthy T-cells to exosomes from malignant cancer cells and examined the impact. They found that malignant exosomes negatively inhibited the function of healthy cells, and caused early die-off and reduced normal cell increase.
Most importantly, the study also found that malignant exosomes, compared to healthy cell exosomes, have a high concentration of unique proteins. This opened the door for Bracha to develop a potential diagnostic tool. His team is now focused on using malignant exosomes as a biological marker to screen for canine osteosarcoma with a simple blood test. The hope is that this could lead to routine screening by primary care veterinarians that would reveal the presence of osteosarcoma early enough to remove the tumor before it spreads.
The oncology service at the VTH is a member of the Comparative Oncology Trials Consortium which is organized by the National Cancer Institute. This allows pet owners the option of choosing cutting-edge treatment while helping to gather important data on cancer treatment that may benefit both animals and human.
The VTH oncology service is currently enrolling patients in six clinical trials. The hospital also enrolls pets in clinical trials in cardiology, radiology, and other areas of veterinary medicine. To learn more, visit vetmed.oregonstate.edu/clinical-trials.
Clinical Trial of New Cancer Treatment
Doctors at the Lois Bates Acheson Veterinary Teaching Hospital at Oregon State University are enrolling dogs with mammary cancer in clinical trials of a new treatment that eradicates cancer in two ways.
Dogs whose owners are considering standard tumor removal surgery may have the option of a new, guided surgery where the patient receives an intravenous injection of a nanoparticle compound that ‘lights up’ when in contact with cancer cells, letting the surgeon know exactly what tissue to cut out. In addition, following tumor removal, the surrounding tissue will be irradiated with an infrared laser which causes the nanoparticle compound to heat up and kill the remaining cancer cells.
The nanoparticle compound was developed by the OSU College of Pharmacy, and found to effectively cure cancer in mice.
The clinical trials were designed for dogs with mammary cancer in order to create a controlled study. “Whenever you are developing a new treatment you want to start with relatively simple and uniform scenarios and limit variables that could confound your results,” says Dr. Milan Milovancev, a professor and veterinary surgeon participating in the study. However, Milovancev says this new procedure may eventually be most beneficial for treating tumors in challenging anatomic areas like the brain and spine.
The Carlson College of Veterinary Medicine is a member of a national consortium of veterinary oncology centers, managed by the National Institute for Health, that conducts clinical trials in dogs with cancer to evaluate new treatments. The ultimate goal of the consortium is to gathering valuable information that will benefit human medicine as well as improve treatment for animals.
The Carlson College of Veterinary Medicine also conducts clinical trials in cardiology, diagnostic imaging, surgery, and equine medicine. Details about these trials are available at https://vetmed.oregonstate.edu/clinical-trials
Identifying Gut Bacteria May Lead To New Treatment For Diabetes
In the intestines, billions and billions of microbes live and function in a symbiotic relationship with each other, and with human cells. In the past decade scientists have begun to demonstrate the importance of these microbes in digesting food, building our immune systems, maintaining stable glucose levels, and other jobs that are critical to good health.
At the OSU College of Veterinary Medicine, in the Department of Biomedical Sciences, Dr. Natalia Shulzhenko’s lab discovered and documented a three-way interaction, or crosstalk, between the immune system, the intestinal lining, and intestinal microbes. Now she is further investigating how that crosstalk affects Type 2 diabetes.
This could not be done without two important tools provided by OSU. The first is the Center for Genome Research and Biocomputing (CGRB) that allows scientists to identify, through DNA, the massive number of different bacteria in the intestines. “It is one of the reasons I chose to work at OSU,” says Shulzhenko. “They have a very strong genome center in terms of both machines and people.”
The other tool that is vital to Shulzhenko’s work is her clan of germ-free mice that have been raised from birth in a sterile environment. They have no microbes in their guts and very few immune cells. They allow Shulzhenko to study bugs in a controlled environment. “We can introduce one specific microbe that we think is important, and look at exactly what it is doing,” she says.
The microbes in human intestines have many jobs. They play a role in the manufacture of enzymes, vitamins, and other essential nutrients; they produce signaling chemicals that regulate our appetite and digestion; and they influence the immune system.
“These are very complex communities,” says Shulzhenko. “Some of the microbes produce chemicals that are consumed by other microbes. So if you take an antibiotic that kills one of them, another may die too.” Shulzhenko affirms the necessity of antibiotics to fight infectious disease but her work does illustrate the down side of their use. “Antibiotics are great but they cause effects on the microbes that can last for a long time, especially if you take them multiple times.”
The modern diet of high-fat, processed foods can also disrupt the complex community in our gut. It can cause inflammation of the intestines which inhibits the production of antibodies, proteins used by the immune system to identify and neutralize foreign bacteria. We need antibodies because they keep the microbe community under control.
Shulzhenko’s research on the crosstalk between metabolism and microbes showed that lack of antibodies can cause epithelial cells in the lining of the intestines to switch jobs: instead of efficiently processing glucose and other nutrients, under microbial pressure, they take over the immune functions of the missing antibodies.
If antibiotics and modern diet affect intestinal microbes, and disrupt the processing of glucose and other nutrients, it is reasonable to suspect they are contributing factors to the development of Type 2 diabetes, and even obesity. “We don’t know for sure yet, but there are good indications of this from animal studies,” says Shulzhenko. She is looking at the genes of microbes that process nutrients to see what functions they perform and what happens when they get disrupted. “We also want to find bugs that would be beneficial and might decrease levels of glucose in diabetes and metabolic syndrome.”
All this new information about the vast network of microbes in the human digestive system, has led to a boom in the probiotic supplement business. But it’s not that simple. “We need to identify the ones that are really critical. That is the tricky part. It might not be specific species but rather what functions they perform,” says Shulzhenko.
Dr. Shulzhenko’s lab has identified some of the more prevalent microbes, and described their relationship with each other via a map that they call a transkingdom network. Now they are using that map to analyze the impact of specific microbes on glucose metabolism. For example, in a recent study, they found that the microbe Akkermansia muciniphila helps control a protein in the body that causes glucose intolerance. The results of this study could potentially lead to a new probiotic used in a targeted treatment of diabetes.