Category Archives: Medicine

Stories about medical subjects.

New Salmonella Dublin test for milk and cattle available for first time in US

Salmonella can cause serious disease on cattle farms, killing calves, causing cows to abort, contaminating raw milk, and harming humans along the way. While the cattle-adapted strain Salmonella Dublin creeps into the Northeastern US, veterinarians and farmers struggle to catch the bacteria in time to protect livestock because these bacteria often hide dormant in carrier animals, making the strain particularly hard to diagnose.

For the first time in the US, a more useful test for Salmonella Dublin is now available exclusively at the Cornell University College of Veterinary Medicine’s Animal Health Diagnostic Center (AHDC). Cheaper, quicker, safer, and more sensitive, the test detects antibodies rather than bacteria. Traditional bacteriological tests could only identify S. Dublin organisms in sick or deceased animals, missing up to 85% of infections in carrier cattle. The new test reveals carriers, helping farmers and veterinarians monitor infection spread over time and track the impact of control measures in ways that were previously impossible.

Dairy-cows-Pavement“We’re very concerned about this disease spreading east because it could severely harm animal and human health, as well as the livelihoods of dairies in the region,” said Dr. Belinda Thompson, senior extension associate at the AHDC. “Salmonella Dublin is already common west of the Mississippi River, but it’s only recently being recognized in the Northeastern US. We want to be pro-active now to keep it out of our farms.”

In recent years the AHDC has dealt with several high-morbidity and high-mortality outbreaks of Salmonella Dublin in New York and other states. To address the problem before it grows further, Dr. Bettina Wagner, director of the Serology and Immunology Section of the AHDC laboratory, secured the nation’s first USDA permit to import and use the enhanced test.

While Salmonella Dublin usually doesn’t make adults cows very sick, it can wreak havoc on young and unborn calves, particularly in populations like those in the East Coast that haven’t been exposed. Its resistance to many common antibiotics severely limits treatment options and, to make matters even worse, it often presents as respiratory disease, throwing off track veterinarians trained to recognize diarrhea as salmonella’s telltale sign.

“Infected calves often look fine the day before a sudden rapid onset, the next day they look depressed, and the next day they die,” said Dr. Paul Virkler, senior extension associate at the AHDC. “Veterinarians often think it’s something else-. We’ve seen newly infected herds in which every single calf in a particular age group dies. We’re trying to keep this from getting to baby calves, the life and future of a farm, and the animals most at risk.”

People working with cattle are also at risk. All Salmonella strains affect most vertebrates and can jump between species. Even carriers that don’t seem sick can shed bacteria, and people, companion animals, and other livestock can pick up the infection through contact with any bodily excretion.

“People have died drinking raw milk with Salmonella Dublin,” said Virkler. “It’s one of the bad players in raw milk. Pasteurizing milk will kill the bacteria.”
Prior to the new test’s release, testing had to be done animal by animal. The new antibody test can use milk samples straight from bulk milk tanks to find whether a herd has been exposed. It can also work with blood samples and diagnose individuals, helping keep unexposed herds infection-free by removing infected animals and pre-screening new animals farmers are considering buying.

“Herd managers can take preventative measures and help control the infection’s spread by isolating sick calves, pasteurizing milk, managing cattle movement, and improving hygiene,” said Thompson. “But to see if any of this is working, they need a tool to monitor success. We didn’t have that until now. This test will let us learn about the prevalence of Salmonella Dublin on the East Coast and hopefully nip it in the bud.”
cows in field

—–

http://vet.cornell.edu/news/Dublin.cfm

Media Hits:

Cornell Chronicle

http://www.news.cornell.edu/stories/Oct12/SalmonellaDublin.html

Meat Trade News Daily

http://www.meattradenewsdaily.co.uk/news/291112/usa___a_lack_of_understanding_over_salmonella_.aspx

MyScience

http://www.myscience.us/wire/cornell_offers_only_u_s_salmonella_dublin_test_for_cattle-2012-cornell

The Post Standard: Syracuse.com

http://blog.syracuse.com/farms/2012/11/better_test_for_cattle_disease.html

Phys.org

http://phys.org/news/2012-11-cornell-salmonella-dublin-cattle.html

Drovers CattleNetwork.com

http://www.cattlenetwork.com/cattle-news/Cornell-offers-only-US-salmonella-dublin-test-for-cattle-176821551.html?ref=551

Bovine Veterinarian Online

http://www.bovinevetonline.com/news/industry/Cornell-offers-only-US-salmonella-dublin-test-for-cattle-176821551.html

USAgNet

http://www.usagnet.com/story-national.php?Id=2486&yr=2012

Dairy Herd Network

http://www.dairyherd.com/dairy-news/latest/Cornell-offers-only-US-salmonella-dublin-test-for-cattle-176821551.html

Food Safety News

http://www.foodsafetynews.com/2012/11/cornells-new-test-spots-salmonella-in-cattle/

Ithaca Journal

http://www.theithacajournal.com/article/20121111/NEWS01/311110027/Cornell-test-detects-salmonella-cattle?odyssey=mod|newswell|text|FRONTPAGE|p

Before It’s News

http://beforeitsnews.com/food-and-farming/2012/11/cornells-new-test-spots-salmonella-in-cattle-2446024.html

Healthy Cooking News

http://healthycookingnews.blogspot.com/2012/11/cornells-new-test-spots-salmonella-in.html

Beef Cattle News

http://savant7.com/beefcattlenews/

Stop Foodborne Illness

http://www.stopfoodborneillness.org/content/cornell%E2%80%99s-new-test-spots-salmonella-cattle

MeatingPlace

http://webcache.googleusercontent.com/search?q=cache:lnLu6SjDDeMJ:www.meatingplace.com/Industry/News/Details/37578+&cd=2&hl=en&ct=clnk&gl=us

Highbeam Business

http://business.highbeam.com/409224/article-1G1-310739927/cornell-offers-new-salmonella-test-cattle

CABI.org VetMed Resource

http://www.cabi.org/VetMedBeta/news/22617

The Meat Site

http://www.themeatsite.com/meatnews/19365/cornell-offers-us-salmonella-dublin-test-for-cattle

Surprise packages sent by cancer cells can turn normal cells cancerous

Surprise packages sent by cancer cells can turn normal cells cancerous, but Cornell scientists have found a way to keep their cargo from ever leaving port. Published in Oncogene in January 2012, their study demonstrates the parcels’ cancer-causing powers, describes how they are made, and reveals a way to jam production. Treatments that follow suit could slow tumor growth and metastasis, the spread of cancer to new parts of the body.

RedMicrovesicle_000

A cancer cell (bottom right) producing and shedding microvesicles, which travel between cells and attach to a normal cell (upper left) to unload cancerous cargo

Remote recruiting through inter-cellular mail lets cancer cells grow their ranks without having to move. While most cells communicate through a standard postal system of growth factors and hormones, cancer cells and stem cells use bulkier parcels called microvesicles. These big packages are stuffed with unconventional cargo that boosts the survival and growth rates of recipient cells and can dramatically alter their behavior and surrounding environment. The cargo of microvesicles includes unique sets of proteins that often reflect their cell of origin and are capable of completely changing a cell’s form and function.

“Stem cells make microvesicles containing one set of proteins that can help heal damaged tissue, while cancer cells make malignant microvesicles called oncosomes that contain another set of proteins which facilitate the growth and spread of tumors,” said Dr. Richard Cerione, professor at the College of Veterinary Medicine and co-author.

Dr. Marc Antonyak and graduate student Bo Li, co-authors and researchers in Cerione’s lab, examined cells in culture to observe the effects of oncosomes on normal cells. They focused on fibroblasts, a normal cell type that is often found associated with human tumors and helps to facilitate tumor growth.
“We incubated healthy fibroblasts together with aggressive breast cancer cells,” said Antonyak. “Although we’d disabled the cancer cells from forming tumors on their own, they kept pumping out oncosomes. The fibroblasts that were bathed in these oncosomes began turning cancer-like, living longer, growing faster, and forming tumors.”

Using a variety of techniques to parse out participating proteins, including immunoblot analysis, immunofluorecence, and electron microscopy imaging, Antonyak identified each link in this pathway and traced it back to the first: a protein called RhoA that acts like a lever initiating microvesicle production. Cancer cells crank production into overdrive, said Antonyak, but jamming the lever could stop the whole assembly line.

“Even if we immobilize cancer cells, as long as they can make these microvesicles they can continue spreading vital components for the development of cancer,” said Cerione. “It’s clear that microvesicles can change the behavior of cells and play an important part in cancer progression. Treatments targeting the microvesicle production pathway we’ve outlined could have a real impact on slowing cancer progression.”

Microvesicles_000 (1)

 

 

 

 

 

 

 

—–

http://vet.cornell.edu/news/CancerCargo.cfm

 

First total knee-replacement surgery restores young dog’s active life at Cornell

jake-copy_000James Gillette has two passions: hunting and his dog. In an effort to spend time with both, he has dedicated years to training Jake, his chocolate lab, how to retrieve game. Often described as inseparable, Gillette and Jake were just as likely to be wandering through wetlands as they were to be at home until travesty hit both.

In the summer of 2010, Gillette fell so ill that when Jake ran in front of a truck and fractured his knee, it was several weeks before Gillette was well enough to get Jake to a veterinarian. When Jake later arrived at the Cornell University Hospital for Animals (CUHA), he was unable to put any weight on the leg and it looked like it might have to be amputated.
In a first-ever surgery at Cornell, Assistant Professor of Surgery Dr. Ursula Krotscheck and an orthopedic surgeon from Ohio State University led a team of CUHA residents in a total knee replacement surgery, a relatively novel procedure never before performed at Cornell. The surgery team removed pieces of bone around Jake’s knee and constructed components to recreate the joint, giving Jake a second chance at an active life.

jakedog055-copySoon after the surgery in Spring 2011, Jake walked home by Gillette’s side using all four legs.

“Jake has recovered extremely well from what in most cases would have been a crippling injury,” said Krotscheck. “We are one of only five teaching hospitals that have performed this procedure. Our team and Jake’s resilience all contributed to making our first canine knee replacement a success.”

Now a year post-surgery, Jake recently passed his first anniversary check-up with flying colors.

“Look at him run!” said Gillette as he tossed Jake’s favorite toy, spurring the eager retriever into a full sprint. “He’s happy as ever and his leg is like new. Before the surgery he wasn’t using it at all. Now we’re playing and hunting together again.”

jakedog035-copy_000jakedog096_000

—–

College of Veterinary Medicine News
http://vet.cornell.edu/news/Jake.cfm

Ticks untold

Prime suspects in mystery fevers may hold new tick-borne diseases
Suddenly your horse is sick and you don’t know why. She breathes normally but her temperature is rising, her eyes grow yellow with jaundice, she seems depressed, and barely eats. The fever is clear but the cause is not; even the most experienced experts can offer no concrete answers. Eventually the fever fades, but is that the end of whatever caused it or is the source still lurking somewhere inside?

Horse owners across the states are facing this distressing scenario. At the Cornell University Animal Health Diagnostic Center (AHDC), Dr. Linda Mittel fields a growing number of calls about these mysterious fevers of unknown origins (FUOs). Many come from the Northeast, Mid-Atlantic, and Great Lakes areas: the nation’s topmost hotbeds of human tick-borne disease. This pattern led Mittel to suspect that the culprits of the fever caper could be ticks and the difficult-to-diagnose diseases they carry.

“Tick-borne diseases are some of the fastest growing emerging diseases in the United States right now,” said Mittel. “As ticks continue expanding their numbers and geographic range these diseases may affect new areas. We get calls about fevers at broodmare operations, showbarns, and farms where race horses rest or layup, even in areas where they didn’t know they had ticks. But horses moving between states can move ticks with them, and the effects of this movement are starting to show.”

Mittel and colleagues at the AHDC are embarking on a project to find just what diseases ticks in hotbed zones are carrying and whether they are behind the wash of mystery fevers in horses. The study will use samples from horses suffering FUOs to look for bacterial infections known to be transmitted by ticks (Anaplasma, Babesia, Borrelia, Ehrlichia, and Rickettsia) as well as other bacteria known to cause non-respiratory infection in horses (Leptospira, Bartonella, and Neorickettsia.)

These agents are considered emerging infectious diseases in humans, and this will be the first study determining their presence in horses with FUOs. The study will also sample ticks found on or near horses in designated areas to find which pathogens they carry and to potentially discover previously undocumented tick-borne pathogens.

Many tick-borne diseases are sensitive to specific drugs; others are not sensitive to antibiotics at all. Knowing which diseases are at the root of FUOs will help veterinarians treat them effectively. It will also help owners understand how the causes of fevers might impact affected horses’ futures in racing, performance, or showmanship.

“I’m quite excited to start solving the mysteries of these fevers and to possibly uncover new previously unrecognized diseases – in horses and people,” said Mittel. “If these agents are in the horses, humans may also have them without realizing– people who work with these horses might be particularly at risk. Knowing what we’re dealing with here will hopefully solve the mystery of FUOs and help equine and human medicine recognize and address the growing onslaught of tick-borne disease.”

This research is funded by the Harry M. Zweig Memorial Fund for Equine Research.

—–

Dr. Cynthia Leifer honored with 2012 Pfizer Animal Health Award

LeiferDr. Cynthia Leifer, assistant professor of immunology at Cornell University’s College of Veterinary Medicine, has been selected to receive the Pfizer Animal Health Award for Veterinary Research Excellence. The award fosters innovative research by recognizing outstanding research and productivity from a faculty member early in his or her career. Nominees are selected for innovative research relevant to animal health that is likely to make national impact.

Leifer’s research sheds light on the currently cloudy causes of autoimmune disease by uncovering inner workings of the innate immune system. Afflicting one in five Americans, autoimmune diseases include a wide array of disorders from rheumatoid arthritis to the skin disease Lupus to irritable bowel syndrome.

“The immune system fights to protect us against invading microorganisms,” said Leifer. “But it must also recognize what to attack and keep its aggressive responses under control to prevent damaging our own bodies.”

When recognition and regulation fail, the immune system can attack the body and lead to autoimmune disorders. Leifer explores how immune cell receptors affect the way these cells recognize and respond to whatever they encounter, whether it’s a microbial invader or a piece of the self.

“Most innate immune receptors identify microbes by detecting unique structures found only on microbes,” said Leifer. “But some work by detecting structures present in both microbes and the self, such as DNA.”

Focusing her research on one such receptor, Toll-like receptor 9 (TLR9), Leifer recently discovered how TLR9 makes the kind of recognition mistakes that lead to autoimmune attacks, opening the door to new possible autoimmune disease therapies.

“Identifying immune-cell regulation systems may reveal therapeutic targets for managing TLR9 function, leading to new treatments for autoimmune diseases,” said Leifer.

Leifer will present her research at a special seminar to be held in September 2012. At a ceremony that follows she will receive an award of $1,000 and an engraved plaque.

“This is a great honor for Dr. Leifer at this stage of her career,” said Dr. Avery August, chair of the department of microbiology and immunology. “Her cutting-edge work on how the immune system senses pathogens is being recognized, and she will join a distinguished list of Cornell faculty who have received this award. We congratulate her on this great accomplishment.”

—–

College of Veterinary Medicine News
http://www.vet.cornell.edu/news/LeiferPfizer.cfm

 

Flag flown over Afghanistan in honor of Animal Hospital goes on display

 flagA new display featuring a special American flag now adorns Cornell University Hospital for Animals’ waiting room. To express thanks for CUHA’s life-saving services, Jessica and Mark Chamberlin gifted the folded flag to CUHA after Mark returned from military duty in Afghanistan, where he had flown it from a Chinook helicopter in honor of CUHA’s doctors, students, and staff.

While serving as a pilot in Afghanistan from October 2010 to October 2011, U.S. Army Chief Warrant Officer 3 Mark Chamberlin received bad news from his wife back home. Lucy, their husky, had been diagnosed with both acute and chronic liver failure. The prognosis looked bleak but Jessica took Lucy to Cornell to see what could be done.

“A biopsy revealed Lucy had hepatitis, extreme liver inflammation,” said Dr. Andrea Johnston, a third-year resident in Hepatology who led the case. “Much of the damage is irreversible and her liver will never function normally, but we were able to get the inflammation under control and develop a nutritional regime specially adapted to her condition. Jessica and Mark worked diligently with the new diet, home-cooking all the food—it’s clear how committed they are to helping Lucy.”

Lucy’s history of hardship began in an abusive dog yard in Alaska. When she got her foot caught in a chain, her former owners cut it off with a chainsaw and left her without medical care. Animal control officers investigating the dog yard found the injured husky and brought her to the animal hospital where Jessica worked as a licensed veterinary technician.

“It took a week to get the infection under control and we had to amputate her leg,” said Jessica. “I spent so much time with her that I got attached and brought her home. She’s been like a child to us ever since.”

The Chamberlin’s parent-like dedication continued through Lucy’s latest ordeal. On the couple’s 10th anniversary, instead of going on the vacation they had originally planned, Jessica and Mark spent their time in Ithaca supporting Lucy during her biopsy and liver care. After Lucy’s initial recovery, they spent time cooking Lucy’s special diet and nursing her back to health.

Their work paid off, and when Mark returned to Afghanistan to lead the flight mission “Operation Enduring Freedom XI,” he flew a flag from the CH-47F “Chinook” helicopter in CUHA’s honor.

“When we first brought Lucy to Cornell we thought she only had a couple weeks,” said Jessica. “Cornell was able to save our girl, and we wanted to do something special to honor the people at the hospital. We are so grateful that Cornell was an option and that all of the doctors and staff were so kind and helpful in getting Lucy back on her feet. We are honored that Cornell has chosen to display the flag in the lobby.”

The flag is proudly displayed in a wooden plaque along with a certificate signed by Mark Chamberlin and the four other officers who flew during the mission under his command. It can be viewed in CUHA’s waiting room to the right of the reception desk window.

flag

—–

http://www.vet.cornell.edu/news/Flag.cfm

First discovery of cells expelling mitochondria uncovers newfound survival tactic

An ancient union between cell and organelle has shown the first sign of fracture, challenging common conceptions of a primordial partnership all multicellular organisms rely on to live. Cornell researchers have recorded the first direct evidence of cells expelling intact mitochondria, the cellular machinery responsible for energy production.

AAAmitochondria B

An illustrated mitochondrion

Malfunctioning mitochondria produce free-radicals that damage cells, contributing to aging, mitochondrial myopathies, and disorders ranging from schizophrenia, bipolar disorder, and dementia to Parkinson’s disease and multiple sclerosis. The newfound breakup behaviour, described in Mitochondrion 2011 Nov.11(6), may be an early cell-survival strategy to escape the toxic effects of damaged mitochondria.

“It is very surprising to see living cells actively jettisoning vital parts of themselves,” said Dr. Theodore Clark, immunologist at the College of Veterinary Medicine. “This is the first time full mitochondria have been found outside cells and it may account for 15 years’ worth of unexplained data showing mitochondrial DNA and protein in extracellular spaces. We think these cells’ behaviour reveals a newfound survival tactic deeply rooted in evolution.”

Today’s mitochondria evolved from freewheeling bacteria that settled down in other cells two billion years ago. In exchange for food and shelter, the bacteria helped cells break nutrients into energy. These helpful tenants became modern mitochondria: the power-plants inside all cells of nearly every animal, plant, fungus, and protozoan.

Yet domestic disputes over cellular housekeeping may spur divorce, according to findings from Clark’s lab showing mitochondria moving out.

Graduate student Yelena Bisharyan discovered this while studying an unrelated phenomenon: escape stunts of the fish parasite Ichthyophthirius multifiliis. Clark’s lab had observed these parasitic protozoa avoiding destruction by shaking off attacking antibodies and exiting their hosts and wanted to see how they escaped.

“Attacking antibodies bind to the parasite’s cell surface,” said Clark. “We suspected that when antibodies attach, the parasite can shed them by breaking off its surface proteins – sort of like a lizard shedding its tail.”

tetrehymena 2

Tetrahymena, a protozoan, sheds proteins and mitochondria in response to attacking antibodies

Applying antibodies to parasites in culture, Bisharyan observed the reactions of Ichtyophthirius and Tetrahymena, another ciliated protozoan used as a model system to study fundamental biological principles across species.

Using negative staining and electron microscopy techniques, Bisharyan recorded parasites sacrificing their surface proteins to rid themselves of attached antibodies. Yet her images also captured something completely unexpected: intact and fragmented mitochondria coming out of the parasite’s cells.

This surprising finding won Bisharyan an invitation to present at one of the 2011 Gordon Research Conferences, a prestigious international forum showcasing major discoveries across scientific fields.

“Mitochondria experts were very excited to see this,” said Clark. “Over the past 15 years several papers have reported mitochondrial DNA and proteins floating outside mammalian cells. No one knew how or why they got there. What we’ve found in protozoa may help explain similar processes in mammals.”

Mitochondria (m) are pushed to the surface and jettisoned from the cell

mitochondria shed

Mitochondria (red) discovered outside cells

Certain cellular stressors can trigger mitochondrial expulsion, according to Bisharyan’s study. In protozoa, for example, not only antibodies but also heat shock can induce this effect. These stressors elevate calcium levels within the cell, possibly damaging mitochondria and causing them to produce toxic free-radicals.

“Our hypothesis is that mitochondria become poisoned and these protozoa have found a way to rid themselves of the damaged powerplants before they can cause further harm,” said Clark. “We think their behaviour reveals an early adaption to cellular stress that other species may share.”

Mammals and fish parasites may bear little family resemblance these days, but a common ancestor may have equipped both with emergency mitochondria-removal systems. Understanding this process could illuminate new approaches to reducing mitochondria-induced damage in humans and other animals.

———-

Cornell University College of Veterinary Medicine news

http://vet.cornell.edu/news/Mitochondria.cfm

Poisoned and burned puppy recovers with skin flap surgery and honey

aMelanie Miller and her Jack Russell terrier, Branson, were traveling the day after Thanksgiving when Miller noticed something was wrong. Usually jovial, the seven-month-old puppy seemed to fade, his eyes began twitching, and he started tremoring in the car. Miller rushed him to a nearby emergency veterinary hospital, where doctors delivered intravenous medicine just in time to get the seizures under control.

Spoiled fish turned out to be the culprit. Fish can spoil quickly, and Branson had eaten leftover fish that had apparently grown mold laden with neurotoxins. For hours the situation looked uncertain. As soon as they stopped the medicine the tremors would start again, but with care and patience the tremors finally passed.

Yet that was just the beginning of Branson’s troubles.

“I noticed a large discolored patch on his belly that hadn’t been there before,” said Miller. “I wasn’t sure what it could be–maybe a reaction to the medicine? It looked really painful and he didn’t seem happy. When we got home to New York I brought him straight to Cornell.”

Dr. Rebecca Kessler, third-year medicine resident, first saw the case. The oddly rectangular-shaped wound was worsening, turning black and leathery and starting to ooze. Kessler gave Branson pain medicine and antibiotics and took a skin biopsy. The results showed that Branson’s skin had been burned.

fDr. Marc Hirshenson, third-year resident in small animal surgery, removed the dead skin before it could become infected. Using an innovative technique to discourage infection, Hirshenson also applied a special topical treatment called Manuka honey to help heal the wound. Well known for its antimicrobrial properties, honey has been used by many cultures throughout history as a way to treat wounds and ward off infection. Manuka honey is produced by bees that feed on nectar from the manuka tree in New Zealand, and licensed wound-care products around the world use it as a special ingredient.

“There has been some evidence in humans that manuka honey is especially good for healing wounds,” said Hirshenson.

Over the next four days the wound improved, developing “granulation tissue” to help itself heal, a sign of a healthy body recovering. But the burn covered such a large area that it looked unlikely that it would fully close without surgery.

To help close the wound and avoid complications, Hirshenson performed a difficult skin flap surgery alongside Associate Professor of surgery Dr. James Flanders.

“Dogs have extra skin around their flanks, and their skin is relatively elastic,” he said. “We were able to stretch this extra skin to cover the area around the abdomen where Branson’s skin had burned and stitch it together around the middle.”

With careful manipulation of the excess skin they were able to close the wound, and after some rest and recuperation Branson was on his way to a full recovery.

“Our job is to help the body heal itself,” said Hirshenson. “Branson had an amazing attitude the whole time that really shined through. He put up with us for a long time, happy to let us handle him even when he was in pain, and was always enthusiastic about walking and eating. His demeanor contributed a lot to his recovery.”

Branson returned home in early December, where Miller reports he is back to his old self.

—–

http://www.vet.cornell.edu/news/Branson.cfm

Researchers discover what cancer cells need to travel

Feb. 21, 2012

By Carly Hodes

cancer cell

An invasive cancer cell moves with its leading edge.

Cancer cells must prepare for travel before invading new tissues, but new Cornell research has found a possible way to stop these cells from ever hitting the road.

Researchers have identified two key proteins that are needed to get cells moving and have uncovered a new pathway that treatments could block to immobilize mutant cells and keep cancer from spreading, says Richard Cerione, Goldwin Smith Professor of Pharmacology and Chemical Biology at Cornell’s College of Veterinary Medicine.

The study, co-authored by graduate student Lindsey Boroughs, Jared L. Johnson, Ph.D. ‘11, and Marc Antonyak, senior research associate, is published in the Journal of Biological Chemistry (286:37094-37107)

Most adult cells stay stationary, but the ability for some to move helps embryos develop, wounds heal and immune responses mobilize. When migrating cells go astray they can cause developmental disorders, ranging from cardiovascular disease to mental retardation. Metastasis (the spread of cancer from one part of the body to another) also relies on cell migration. How exactly cancer cells migrate
and invade tissues continues to be a mystery. However, Cerione’s lab uncovered a potentially important clue when it noticed that cancer cells gearing up to move would collect a protein called tissue transglutaminase (tTG) into clusters near the cell membrane.

meta“TTG is turning up in many aspects of human cancer research and seems to be contributing to the process that turns cells cancerous,” said Cerione. “Lindsey and Marc discovered that cells must gather tTG into a specific place in their membrane before they can move. But tTG is usually inactive, and we’ve been trying to understand how a cell gets this protein to the exact right place so that it can be activated to stimulate cell migration.”

Observing breast-cancer cells in culture, Cerione’s lab found a missing link in our understanding of cell migration: Cancerous cells become hyperactive invasion vehicles by using tTG together with other proteins like wheels, poking them through the surface to form a “leading edge” that pulls the cell forward. But to get the wheels to the leading edge, it turns out they need another protein to roll them there – a “chaperone” protein called heat-shock-protein-70 (Hsp70).

“We’ve known for years that Hsp70 acts as a chaperone to other proteins, ensuring that they assume the right structure and behave properly when a cell is under stress,” said Cerione. “Heat shock proteins have also been implicated in cancer, although scientists have been trying to understand their exact role in cancer. Our research has uncovered a previously unknown role for these chaperones – helping tTG get to the leading edge. TTG must be in this location for cancer to spread.”

migrating cervical cancer cell

A migrating cervical cancer cell stained for tissue transglutaminase (green). Cells must gather this protein at their leading edge in order to move.

When cells become stressed, Hsp70 influences the behavior of their “client” proteins, ensuring they keep the right shape. Cells need chaperones like Hsp70 to ensure that various proteins work correctly and don’t warp, but these same chaperones can help cancer cells spread by helping move tTG to the membrane surface. Using inhibitors that block the function of chaperones, Cerione and his team paralyzed Hsp70s and stopped breast cancer cells in culture from gathering tTG into a leading edge, effectively immobilizing them.

Exactly how Hsp70 gets tTG going remains unknown, but Cerione believes other proteins are involved.

“If we can better understand how Hsp70 influences tTG, we can figure out ways to modulate that interaction to immobilize cancer cells and keep them from becoming invasive,” said Cerione. “We suspect Hsp70 is using a third kind of protein to move tTG, and that’s what we’re trying to figure out now. Finding the next link in this chain of events could have important consequences for preventing cancer migration and metastasis.”

Carly Hodes ’10 is a communication specialist at the College of Veterinary Medicine.

—–

Original Press Release:

Cornell University College of Veterinary Medicine news

http://www.vet.cornell.edu/news/Migration.cfm

Media Hits:

Cornell Chronicle

http://www.news.cornell.edu/stories/Feb12/CancerMovers.html

Ithaca Journal

http://www.theithacajournal.com/article/20120222/LIFE/202220336/Cornell-scientists-find-cancer-cells-need-travel?odyssey=mod|newswell|text|Life|s

PhysOrg

http://www.physorg.com/news/2012-02-cancer-cells.html

ECNMag

http://www.ecnmag.com/News/Feeds/2012/02/blogs-the-cutting-edge-researchers-discover-what-cancer-cells-need-to-tra/

Zeit News

http://www.zeitnews.org/biotechnology/researchers-discover-what-cancer-cells-need-to-travel.html

My Science

http://www.myscience.cc/news/2012/what_cancer_cells_need_to_travel-2012-cornell

Reddit

http://www.reddit.com/r/science/comments/q0swt/cancer_cells_must_prepare_for_travel_before/

Laboratory Equipment

http://www.laboratoryequipment.com/news-Proteins-Key-to-Stopping-Cancer-from-Spreading-022312.aspx

Conservation in action

First Indonesian to receive major fellowship will help save world’s rarest rhinoceroses

Deep in the Indonesian rainforest on the island of Java roam the last of earth’s most critically endangered large mammal species: the Javan rhinoceros. Once Asia’s most widespread rhinoceroses, these secretive forest-dwellers disappeared altogether from the continent’s mainland in October 2011, when the last individual was found dead in Vietnam with its horn chopped off by poachers. A single population of just 40 rhinoceroses survives in the western half of Java’s Ujung Kulon National Park, cramped into a corner of the island that has reached its carrying capacity.

The Indonesian government recently endorsed a daring plan to expand the range of their emblem species by establishing a second population with more room to grow. Yet a major concern remains. The plan involves moving some rhinoceroses from the isolated westernmost tip of Java to the eastern side of the park—an area surrounded by 19 agricultural villages whose inhabitants rely on water buffalo to work their rice paddies. No fences limit the wanderings of these loosely managed buffalo, which regularly pass into the park and could spread diseases that would quickly decimate the rhino’s population.

Cornell postdoc Dr. Kurnia Khairani has received a Fellowship Training Grant from the Morris Animal Foundation to address this problem. With the help of faculty and students at the College of Veterinary Medicine, Khairani is combining fieldwork in Indonesia with labwork and training at Cornell to improve the health and outlook of Javan rhinoceroses. It is the first time an Indonesian has received this prestigious award, and the first time a Cornell fellow will be trained in conservation medicine.

“Of the five rhinoceros species the Javan is the rarest, and Khairani’s work is critical to its future,” said Dr. Robin Radcliffe, director of the Cornell Conservation Medicine Program, one of the world’s foremost experts working in rhino conservation. Radcliffe oversees the project and is excited by its possibilities. “Khairani herself is a major investment for conservation efforts in this region: she will take her Cornell training back to Indonesia and become a decision-maker in her own country. Cornell is involved in real-world conservation, training people who will use what they learn here to tackle new problems in the race to preserve biodiversity.”

A postdoc in the laboratory of immunologist Dr. Julia Fellipe, Khairani will work under the joint mentorship of Fellipe and Radcliffe. Additional mentorship from epidemiologist Dr. Daryl Nydam and microbiologist Dr. Pat McDonough will round out Khairani’s skills.

Conducting a preliminary health survey of village buffalo, Khairani found several diseases of concern to rhinoceroses, including blood parasites, salmonellosis, and leptospirosis. With highly infectious diseases such as SARS, West Nile Virus, and Avian Influenza making worldwide headlines for crossing species barriers and ecosystems, it is critical to get this historic move of the rarest rhinoceros right the first time. Khairani’s ongoing survey will focus on hemorrhagic septicemia, a bacterial disease linked to four recorded die-offs of Javan rhinoceroses in the region. Khairani will determine the prevalence, distribution, and risk of contracting septicemia faced by the buffalo population; conduct questionnaire-based interviews with buffalo owners to determine management factors that might contribute to the regional epidemiology of the disease; and propose possible interventions.

The project also involves outreach, educating local public health officers and villagers on septicemia diagnosis and management through hands-on training. It has also opened doors for Cornell veterinary students to gain valuable hands-on international experience, and several have already conducted internships in Indonesia with Khairani through Cornell’s Conservation Medicine Program with funding by Expanding Horizons.


“Knowledge of the region’s diseases will help veterinary officers improve the health of buffalo, a resource crucial to the region’s economic vitality,” said Khairani. “Healthier buffalo will enhance the well-being of local villagers while reducing their impact on the park. Improving our understanding of animal health in the area will help reduce the risk of disease transmission from livestock to rhinoceroses. This is essential to establishing a second habitat and population of the rare Javan rhinoceros, a crown jewel of Indonesia’s amazing biodiversity.”

‘Scopes Magazine
February 2012