PVM Cancer Researcher Collaborates on Creating Device to Identify Risks for Breast Cancer

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Dr. Sophie Lelièvre, professor of cancer pharmacology in the Purdue University College of Veterinary Medicine.

Purdue University College of Veterinary Medicine Professor of Cancer Pharmacology Sophie Lelièvre is moving mountains with her contributions to breast cancer research.

Dr. Lelièvre, a faculty member in the College’s Department of Basic Medical Sciences, heads up research concerning nutritional effects on breast cell biology and now is working on a project to create a device that could help identify risk factors that cause breast cancer. Called “risk-on-a-chip”, the device itself is a small plastic case with several thin layers and an opening for a piece of paper where researchers can place a portion of tissue. This tiny environment produces risk factors for cancer and mimics what happens in a living organism.

Dr. Lelièvre puts an emphasis on the importance of the most critical window of time for breast cancer prevention: before birth leading all the way up to puberty. “We want to be able to understand how cancer starts so that we can prevent it,” she said.

Cancer is a disease of gene expression, and organization of genes is specific to a particular species and organ, which means it wouldn’t be useful to perform this study on rats or mice. Thus, Dr. Lelièvre needs a model that will mimic the organ in question. She teamed up with Dr. Babak Ziaie, professor of electrical and computer engineering at Purdue, to create the device.

“Unlike conventional 2-D monolayer cell culture platforms, ours provides a 3-D cell culture environment with engineered gradient generators that promote the biological relevance of the environment to real tissue in the body,” said Rahim Rahimi, a graduate student in Dr. Ziaie’s lab.

Demonstration of concentration gradient in microfluidic system using red and blue color dye solutions.

The risk-on-a-chip is based on an earlier cell culture device developed by Drs. Lelièvre and Ziaie to study cancer progression. To modify it for prevention, Dr. Ziaie plans to add nanosensors that measure two risk factors: oxidative stress and tissue stiffness.

Oxidative stress involves a chemical reaction that occurs as the result of diet, alcohol consumption, smoking, or other stressors, and it alters the genome of the breast, aiding cancer development. The risk-on-a-chip will simulate oxidative stress by producing those molecules in a cell culture system that mimics the breast ducts where cancer starts.

Tissue stiffness refers to the stiffness of breast tissue, which has been found to contribute to onset and progression of breast cancer. The research team will measure stiffness within a tunable matrix made of fibers, whose density is relative to stiffness.

Breast cancer is particularly difficult to prevent because multiple risk factors work independently or in combination to promote disease onset. To account for this, the risk-on-a-chip will be tailorable to different groups of women at-risk.

“We need to see if there’s a difference in primary cells from Black women or Asian women or White women, because that matters,” Dr. Lelièvre said. “The way our genome is organized depends on an individual’s ancestry and lifestyle; it’s very complex. That’s why cancer is so difficult to treat.”

The research team believes the risk-on-a-chip could be used to study additional risks by adding more cell types and biosensors. They estimate that optimization for each new condition will take between six months and a year.

Drs. Lelièvre and Ziaie have received a joint grant from the Department of Defense to create and test the device with structures that mimic the mammary gland.  The grant will provide more than $500,000 over the next two years.

This project is part of the International Breast Cancer and Nutrition collaboration (IBCN), which involves a group of multidisciplinary research teams that seek to elucidate the common link between nutrition and breast cancer. Launched at Purdue University, IBCN is the first dedicated worldwide effort in exploring the links between diet, the genome, and the risk of breast cancer.

Writer(s): Purdue Veterinary Medicine News | pvmnews@purdue.edu

Purdue Veterinary Medicine Equine Specialist Researches Better Treatments for Sepsis in Horses Using Innovative, Multimodal Approach

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A foal undergoes treatment for sepsis at the Purdue University Large Animal Hospital.

Sepsis is a common cause of illness and death in both humans and animals worldwide, and occurs when infection leads to overwhelming, whole-body inflammation. In the majority of cases, infections resolve quickly by the use of antimicrobial drugs such as antibiotics, but widespread inflammation can lead to shock, organ failure, and death. Developing new therapies that stem the harmful cascade of inflammatory events is vital to improving survival in septic patients.

Dr. Sandra Taylor, associate professor of large animal internal medicine in the Purdue University College of Veterinary Medicine, is conducting research aimed at improving treatments for sepsis in horses. Newborn foals and other large animal species are particularly susceptible to sepsis when colostrum (the mother’s first milk) is not ingested within a few hours of birth. Colostrum contains protective antibodies that are critical in preventing ingested bacteria from entering the blood stream and causing sepsis.  Adult horses also suffer from sepsis, which can occur in cases of severe pneumonia, colitis, or uterine infection.

Dr. Taylor’s love for animals, particularly horses, led her to pursue a career in veterinary medicine. “While investigating an equine model of HIV during graduate school, I developed a passion for research,” Dr. Taylor said. “I am especially interested in research that can be applied to both animals and humans.” Equine studies can be good examples of that kind of comparative research, according to Dr. Taylor.

Dr. Sandra Taylor, associate professor of large animal internal medicine in the Purdue University College of Veterinary Medicine, with a newborn foal.

Specifically, Dr. Taylor has studied the anti-inflammatory effects of ketorolac tromethamine (KT) in the horse, and has found that this non-steroidal anti-inflammatory drug (NSAID) decreased inflammation in equine blood that had been stimulated with gram negative bacteria. She is currently investigating the analgesic properties of KT, phenylbutazone (Bute), and flunixin meglumine (Banamine®) in the horse. She hopes that KT will be a superior NSAID in treating both sepsis and pain in horses.

Dr. Taylor is also investigating the safety and efficacy of using stem cells to treat sepsis. Stem cells have been shown in her laboratory to elicit anti-inflammatory effects in bacteria-stimulated equine white blood cells, and in rodent models (mice and rats). Dr. Taylor has isolated and grown stem cells from horse blood, and is currently in the process of characterizing the cells prior to confirming the safety of intravenous administration. The next step will be to test the ability of stem cells to improve survival in septic horses.

Writer(s): Aparna Desai | pvmnews@purdue.edu

Rare Case Leads ADDL Resident to First-time Discovery in White-tailed Deer

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When Dr. Andrea Vanderpool (PU DVM 2004), resident in anatomic pathology at the Indiana Animal Disease Diagnostic Laboratory, received a biopsy submission of a farmed deer in Indiana, she wasn’t aware she was looking at a landmark discovery.

The deer died from chronic bacterial pneumonia, which is common, but the referring veterinarian noticed that the deer’s front and rear limbs were swollen as well. The swelling wasn’t edema, although edema would have made sense as a symptom resulting from pneumonia. In this case, it was bony thickening of all four limbs.

Hypertrophic osteopathy was the eventual diagnosis. There is no previous record of this condition being seen in a white-tailed deer. Commonly seen in dogs, and sometimes humans, hypertrophic osteopathy occurs when lesions in the lungs lead to production of new bone on the distal limbs. “There are a number of theories why this might occur,” said Dr. Vanderpool, “but why something in the chest leads to increased growth factors in the limbs is still unknown.”

There are very few known cases of hypertrophic osteopathy in other deer species, with one reported in a deer species in Europe.

“That this is even a possibility is fascinating to the veterinary community,” said Dr. Vanderpool. “It helps to know that this is an entity that exists in deer, and that we might look out for symptoms in our cases moving forward.”

Dr. Vanderpool earned her Purdue DVM degree in 2004. Following graduation, she worked in small animal private practice in Indiana and Tennessee, before returning to Purdue to begin her residency and graduate teaching assistantship in the Department of Comparative Pathobiology.

Writer(s): Lauren Bruce | pvmnews@purdue.edu