Category Archives: Cancer

First proven ovarian cancer origin could unlock earlier detection in many human cancers

c
A very large ovarian cancer as seen on CT

The most common and aggressive type of ovarian cancer, ovarian carcinoma, leaves a dark trail. Science has learned too little and most women learn too late to treat the deadly disease.

Cornell scientists have found ovarian carcinoma’s first proven origin cells and uncovered clues for finding similar sources of other cancers. Published in Nature in March 2013, the study opens paths for new screening methods to detect cancer earlier and increase treatment chances in the ovaries and beyond.

Most organs have stem-cells, which help healing and development, but many cancers start when such cells go astray. Using a novel cell location technique never before used in ovaries, the Cornell study uncovered a nest (niche) of particularly cancer-prone stem cells at an area in the ovaries where different tissue types meet. It provides the most direct proof yet that vulnerable stem cells can nest near such tissue junctions, which occur throughout the body.

“Poor understanding of ovarian cancer’s development has posed the biggest roadblock to helping its victims,” said Dr. Alexander Nikitin, pathology professor at Cornell’s College of Veterinary Medicine and leader of the Cornell Stem Cell Program. “We have found what is very likely to be the source of cells from which ovarian carcinoma arises, as well as the strongest suggestion yet that cancer-prone stem cells can nest in tissue junctions. This could spur new discoveries of cancer-prone stem cell niches throughout the body, revealing new ways to screen for and diagnose several different cancers.”

c
Stem cells expressing stem cell marker ALDH1 (red) and retaining proliferation label BrdU (green) in the hilum region of the ovary

A woman’s risk of getting aggressive ovarian cancer in her lifetime is about 1 in 72, according to the American Cancer Society. Once diagnosed, 70% will die within five years. No good screening tests exist, but uncovering a specific location that seeds it could let people catch it earlier and change those chances for the better.

Nikitin’s lab found the new cancer-prone stem cell niche using direct lineage tracing, a new technique that labels and tracks cells. The niche, found near the junction of the ovaries and the uterine tube (also known as the Fallopian tube), houses stem cells that regenerate the ovarian surface epithelium, a cover that opens when females ovulate and must grow back each time.

But Nikitin’s team found that these cells turned cancerous when two important tumor suppressor genes p53 and Rb were deleted. These genes have been shown to be inactive in human ovarian carcinoma. Nikitin’s lab had previously proven that properly functioning p53 and Rb protected against ovarian carcinoma development in the mouse.

The new study showed that newly discovered stem cells without p53 and Rb grew faster and showed more aggressive metastatic behavior compared to more mature cells. Nikitin is now working on leveraging his lab’s discoveries to find cancer-prone stem cells at similar junction areas in human ovaries and other places where two different types of tissue converge, such as the esophagus and stomach, anus and rectum, and different parts of the uterus. Such junctions are breeding grounds for tumors.

“Until now, we have had no explanation for why so many tumors form at junction sites,” said Nikitin. “Our study suggests new undiscovered stem cell niches might occur beyond the ovaries. It’s likely to lead scientists to search for similar cancer-prone stem cell niches at other junctions, which could lead to specific diagnostic screening tests to detect cancers earlier.”

Published 3/7/13

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

 

Canine cancer-survivor treated at Cornell continues champion career

dogGarnering top honors in his field despite battling two deadly canine cancers, a Cornell family’s dog treated at the College of Veterinary Medicine has become an emblem of hope for patients and pet-owners facing terminal illness. Through expert treatment, family support, and a hardworking spirit, this resilient survivor continues to succeed in a multifaceted sporting career while defying cancer’s odds.

Hokey is a Belgian Tervuren, an energetic breed born to work. This put him right at home in a family full of Cornellians, including Dr. Debra Eldredge DVM ’80/BS ’76. A retired veterinarian-turned-dog-trainer, she brought Hokey toward the top ranks in agility, obedience, herding, and tracking. Then one day in September 2009, just after a successful competition, lymph nodes across his body suddenly swelled. A biopsy at Cornell revealed that Hokey had aggressive lymphoma, an immune-cell cancer with a median survival time of one year.

“I drove him to Cornell’s animal hospital to discuss chemotherapy,” said Eldredge, who began treatments in consultation with canine cancer experts in Cornell’s oncology service. “He flew through without a bump and earned the highest level title in agility that year. He especially loves tracking, and chemo can destroy the sense of smell. Yet I had faith in Hokey’s abilities, and we continued training.”

Testing a champion

They entered a Variable Surface Tracking (VST) test, the American Kennel Club’s most difficult competition. A dog must follow a person by scent over a multi-terrain track three to five hours old and locate three dropped items, all with no handler guidance. Only about 300 dogs in the world have passed this grueling test—three of them trained by Eldredge and her two children, current Cornell students.

dog“Hokey got into a night test and tracked right off – down cement stairs, through a large crowd leaving an awards ceremony, across a courtyard, finding all articles in the dark. He was the first dog ever to pass at that site,” Eldredge said. “That Summer he earned his Companion Dog Excellence in Obedience (CDX) title and in December we tested for Tracking Dog Excellent (TDX) certification. It was sleeting hard. Hokey took us across a creek, through brush, woods, and swamps, over a horse jump, and finally onto a muddy path where he found the final item.”

Hokey became the 280th Champion Tracker ever in the history of AKC – with all the most difficult tests passed post-chemotherapy. His high profile in the sport-dog world as champion athlete and cancer survivor brought hope to communities across the country. A certified therapy dog, Hokey has been a special guest in many cancer fundraisers, and is pictured on a bumper sticker bearing the slogan “Canine Cancer Survivors Can Do.” In April 2010 he was named “Top Companion Dog” by Freedom Guide Dogs, “chosen for his accomplishments and perseverance in the face of a serious obstacle.”

New cancer, same resilience

After two healthy years, Hokey developed a troubling sneeze in October 2011. Eldredge found a tumor in the left side of his nose caused by a new type of cancer: nasal chondrosarcoma.

“Dogs developing this nose cancer usually survive approximately one year,” said Dr. Margaret McEntee, the Alexander de Lahunta Chair of the Department of Clinical Sciences and Section Chief of Oncology at Cornell’s animal hospital. “Nasal tumors are especially difficult to cure—they require aggressive radiation therapy that can also affect nearby normal tissues with temporary side effects.”

dogUsing a CT scan to create 3D maps of his nasal cavity, Cornell’s oncology service developed a detailed treatment plan targeting the tumor in a way that would minimize normal tissue damage. Hokey began a course of 19 daily radiation treatments using Cornell’s linear accelerator. Throughout this he was surrounded by friends —partly because he makes them so easily.

“It’s a very hard course for patients but Hokey’s amazing attitude won over everyone he came across,” said McEntee. “Technicians and students visited him frequently; he even helped ease other nervous patients who came through. Having happy dogs around brightens everyone’s days.”

After radiation and recovery from minor side-effects to his eyes which Cornell ophthalmologist Dr. Thomas Kern described as “miraculous,” Hokey returned home.

“The left side of his face suffered cosmetic side-effects but he’s healing quickly– never missing a meal,” said Eldredge.  “He competed in obedience again this month and loves to be back to work. His genetics must stink for him to get two cancers but his love of life and healing powers are strong.”

Hokey has donated blood to the DNA bank at Cornell, where it will contribute to cancer research in dogs and humans.

—–

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

http://blogs.cornell.edu/theessentials/2012/02/13/hokey%E2%80%99s-triumph/