Human, animal doctors report success in dog's open heart surgery
By Sarah Carey
GAINESVILLE, Fla. - When veterinarians and cardiologists from the University of Florida said "Yankee, go home" this week, they did so with pride and a sense of heartfelt joint ownership.
Yankee, a tail-wagging, 7-year-old yellow Labrador retriever, went home from UF's Veterinary Medical Center today (Feb. 3) with her actual owners, the Stazzone family of Satellite Beach, after successful open heart surgery to remove a bamboo barbecue skewer from her heart.
In a collaborative procedure involving UF veterinarians and physicians from the Congenital Heart Center at UF, Yankee was placed on bypass for 55 minutes Jan. 27 at a surgical research facility located near the MRI unit that was used to pinpoint the skewer's location. The skewer had perforated the dog's stomach and pierced the heart after she ate a steak kabob.
The entire operation lasted about three hours, and pediatric cardiothoracic surgeon Mark Bleiweis, M.D., the center's director, was lead surgeon on the case.
"We had very little time to coordinate this thing, and the team worked out really great," said Gary Ellison, D.V.M., a professor of small animal surgery at UF who assisted in the procedure. "While we provided the critical care before and after Yankee's surgery, we don't have the capability of doing bypass at our veterinary hospital and we needed the human surgeon's expertise."
Only two veterinary institutions in the country perform heart bypass procedures in dogs and those are located in Texas and Colorado, Ellison said, adding that Yankee's condition would have made transport to any other facility extremely risky.
Once the skewer was removed, Bleiweis rebuilt a damaged heart valve.
"I'm really proud of what we did, and that we were able to put this many people from so many specialties together to save this dog's life," Bleiweis said. "I'm an animal owner and this is someone's family member."
Bleiweis added that although Yankee had a severe heart infection, she responded to the procedure "better than most people do."
"We were able to get her off the ventilator and out of the operating room without a problem and she was standing on all fours that same day," he said. "It was amazing."
After the operation was completed and Yankee awakened from the anesthesia, she was transported back to the VMC's small animal intensive care unit, where she continued to recuperate this past week.
"By Sunday night, she was eating and walking outside," said Nikki Hackendahl, D.V.M., the small animal internal medicine resident at UF who had primary responsibility for Yankee and monitored her progress every day.
Yankee's woes actually began on Halloween, when the Stazzones had steak kabobs for dinner and Yankee grabbed one, "practically inhaling the whole thing," Mary Stazzone said. "Immediately she was sick and throwing up, and everything I cleaned up was steak, but no stick."
After her initial surgery, Yankee seemed to have recovered. But two months later her condition rapidly deteriorated and it initially appeared to be unrelated to her previous illness.
When Yankee was admitted to the VMC a few days prior to surgery, her blood was not clotting and she was anemic, Hackendahl said. Then Hackendahl detected a heart murmur and immediately requested a consultation from veterinary cardiologist Amara Estrada, D.V.M.
"We did an echocardiogram and noticed a strange linear structure in the heart," Estrada said. "Then we found out the dog had a history of eating a bamboo skewer back in October and surgery had been performed to remove part of it from the dog's stomach."
The veterinarian who referred Yankee to UF had performed a CT scan and been extremely thorough, but wood is not visible on a CT scan, Hackendahl said.
Thankfully, Dr. Hackendahl discovered the heart murmur," Stazzone said. "We knew there was a slim chance this would all work out, but we did a lot of praying on this one. We obviously love Yankee very much."
Because of the close relationship Estrada and the veterinary cardiology group have with the human pediatric cardiology team - the two groups round together on Wednesdays - Estrada shared images from Yankee's echocardiogram and asked her human counterparts' opinion.
"We were going to do inflow occlusion, a procedure that prohibits blood flow but gives you only two to four minutes to open up the heart and look inside," Estrada said. "They said this wasn't such a great idea due to the short time frame and the limited access. I asked them for help and they readily accepted and offered to assist us with the case."
Also playing a key role from the veterinary college were numerous other clinicians, including Hackendahl, small animal medicine associate professor Julie Levy, D.V.M., Ph.D., anesthesiology resident Andre Shih, D.V.M., and cardiology resident Herb Maisenbacher, D.V.M. Assisting from the College of Medicine were Barry Byrne, M.D., Ph.D., a professor and associate chairman of Pediatricsdirector of the Powell Gene Therapy Center at UF; Harvey Ramirez, D.V.M., from UF's laboratory animal services; and Dale Clark, a blood perfusionist. Behind the scenes, many others, including veterinary college faculty and staff who operate the small animal hospital's blood bank, worked overtime to obtain blood components and coordinate what was necessary to complete the procedure.
Although Yankee developed a systemic infection that will continue to be treated with antibiotics, she's alive and improving every day, clinicians said. Her owners said their three daughters have been making cards for Yankee and can't wait to have her home.
"I bought Yankee for my husband when we were just dating and we've had her for seven years," Mary Stazzone said. "It was just such a shock how this has all happened
Molecular force field helps cancer cells
defend against attack
By Melanie Fridl Ross
GAINESVILLE, Fla. - Much as the famed starship Enterprise would deploy a deflector shield to evade enemy attack, tumor cells are capable of switching on a molecular force field of their own to fend off treatments aimed at killing them. Now University of Florida researchers have found a chink in their armor.
The cells churn out an enzyme that bonds with a protein, creating a protective barrier that deflects damage from radiation or chemotherapy and promotes tumor cell survival. But in laboratory experiments, UF scientists were able to block the union, and the malignant cells died. The findings are opening new avenues of research that could lead to improved cancer therapies, the researchers report this week in the journal Cancer Research.
"We have found a gene called focal adhesion kinase which is produced at very high levels in human tumors, and our work has shown this makes the tumors more likely to survive as they spread throughout the body and grow," said William G. Cance, M.D., a researcher at the University of Florida Shands Cancer Center and chairman of the department of surgery at UF's College of Medicine. "It also makes them more resistant to our attempts to kill them. And we're trying to understand exactly why this gene, which is a small enzyme molecule, is very intimately associated with tumor cell survival."
Focal adhesion kinase, or FAK, is commanding increasing attention and has spawned a flurry of research designed to develop new drug therapies, said Cance, who is known internationally for his genetic investigations of tumor survival. These medicines would prevent FAK from linking with the protein known as vascular endothelial growth factor receptor 3, or VEGFR-3. The protein is tied to the growth of channels in the lymph system that serve as cellular superhighways for cancer spread and is found in breast, colon and thyroid tumors.
Cance and colleagues were the first to pull FAK out of human tumors and to show that human cancers make the molecule in large quantities. In 1996, the team was the first to show that if a tumor is prevented from producing the enzyme it dies. The scientists also have identified some protein receptors FAK binds to; VEGFR-3 is the latest they've discovered and represents a "hot area for developing therapeutics," Cance said.
"We've shown that if you disrupt this interaction - if you block the binding of these two proteins - the tumor cells are more prone to being killed," he said.
UF researchers identified FAK's interaction with VEGFR-3 in cell cultures of human breast cancer. Breast cancers that pump out high volumes of FAK and VEGFR-3 are more aggressive tumors, Cance said. The scientists were able to block FAK from binding with VEGFR-3 by introducing a different protein that stopped cancer cells from dividing and caused them to die but spared normal breast cells.
"FAK is a critical molecule, and in the future different ways of targeting either the enzyme itself or targeting the binding between these various proteins will have a major impact on cancer, I believe," Cance said. "We think it's one of the Achilles' heels for tumor cells and you can disrupt it in a number of different ways. For example, we might be able to design drugs that mimic this area of binding and disrupt it in patients."
Because normal cells generate much lower levels of FAK than tumor cells do, treatments could be developed to target FAK and VEGFR-3 at dosages markedly less toxic to healthy tissues yet lethal to cancer.
"We have a therapeutic window," said Cance, the study's senior investigator. "In normal cells we've shown you can knock it out and cells can still resist the loss of expression of focal adhesion kinase, whereas the tumor cells use it as one of their major proteins for survival."
UF surgical resident Christopher Garces, M.D., and UF research assistant professors Elena Kurenova, Ph.D., and Vita Golubovskaya, Ph.D., also were involved in the work, funded by the National Cancer Institute.
"We take our patients, we look at their tumors and we try to find clues to why their tumors grow, why their tumors spread, and we look at the various genes and proteins that make their tumors what they are," Cance said. "So from the patient's standpoint, the more that we can characterize their tumor and understand why it behaves like it does, the greater chance we'll then be able to go back to the patient with therapeutics, and that laboratory bench to bedside is what our researchis all about."
H. Shelton Earp III, M.D., director of the Lineberger Comprehensive Cancer Center at the University of North Carolina-Chapel Hill, said, "The Cance lab finding follows on their groundbreaking work showing that human tumors survive in part by overexpressing FAK. This current discovery provides an important clue as to how to exploit this overexpression for the therapy of human cancers."
Steven Frisch, a professor of biochemistry and molecular pharmacology at West Virginia University, said the research raises "the compelling possibility of targeting FAK for a novel cancer therapy."
"FAK plays a major role in the survival of tumor cells in their normal attached state, and, when over-expressed or hyperactivated, it opens a molecular gate that allows tumor cells to detach and metastasize," Frisch said. "The Cance lab's new observations on the VEGFR3-FAK interaction are both of interest for understanding the functions of these two pivotal molecules in cell behavior, as well as sharpening the focus of FAK-based drug discovery efforts to control cancer."