Human breast cancer cells (left) are treated with a trial dose of the leukemia drug dasatinib (center) and then with a 10-fold stronger dose. (Image courtesy of Seth Corey), August 30, 2010, by Jessica krinke  —  Researchers at Northwestern University are pioneering ways to shoot out the tires from breast cancer’s getaway car in a high-speed chase of drugs and carcinogenic criminals.

That’s because breast cancer itself doesn’t kill until it metastasizes, or travels, to other sensitive organs, invades and then grows. But a new clue to stopping this destructive spree surprisingly came from pediatric research.

Dr. Seth Corey is a pediatric oncologist at Children’s Memorial Hospital and professor of cellular and molecular biology at Northwestern University’s Feinberg School of Medicine. They’ve found that dasatinib, a drug already used to eliminate leukemia in the bone marrow, may also prevent mobility in breast cancer, keeping it from invading vital organs.

But even though dasatinib is FDA-approved for the treatment of leukemia, the likelihood of your doctor prescribing it for breast cancer just yet is slim. The Northwestern research team hopes that dasatinib’s clinical trials will help determine what kinds of breast cancer respond to it best. By mapping the biological signatures of varying cancer types this way, fingerprints of these malignant flight-risks to assist in diagnosis and further targeted treatment may not be far off.

Seth Corey (image courtesy of Jessica Krinke/MEDILL)Medill Reports asked Corey about his team’s research, and what the future may hold for dasatinib and breast cancer.

Q)        What is the basic aim of your research?
A)   My primary interest is in leukemia, which is a cancer of the bone marrow – the site of [all] blood cell production. Cancer cell behavior is this: they proliferate, they do not differentiate, and they do not die. But for solid tumors, which is everything but leukemia, the cancer cells also have additional characteristics that make them malignant, and that is the ability for them to invade local tissues, spread to different sites and to metastasize as in the liver, the bone, the brain. Those are the more common sites for breast cancer metastasis.

Q)   What makes breast cancer unique among cancers?
A)   I’m a pediatric oncologist, and even though death due to cancer remains the most common cause of non-accidental death in children and adolescents, it’s uncommon. Maybe about 12,000 cases of new pediatric cancer are diagnosed each year in the United States. The total for adult cancers is about 1.5 million people each year. 

Every cancer is different, and even within different [cancers] there are different types and different levels of aggressiveness. Breast cancer is a public health concern because around 180,000 women are diagnosed each year, so it’s one of the most common cancers to occur.

Q)   Is leukemia a very common cancer in children?
A)   Acute lymphoblastic leukemia (ALL) is the most common type of childhood cancer, although in adults it’s very rare. ALL occurs with about 3,500 cases per year, so it’s a little less than a third of all pediatric cancers.

ALL has been the focus in childhood cancer and, over the past 40 years or so, it has gone from a disease that was almost uniformly fatal to a disease that’s almost uniformly curable. We’ve gone from a roughly five-year survival rate in about 1960 or so of 8 percent to a five-year survival rate in 2010 of like 90-92 percent. It’s been an achievement of modern chemotherapy.

Q)   So how did leukemia in children lead you to study breast cancer?
A)   Christina Pichot gets a lot of the credit for helping to steer the lab and my thoughts in the direction of breast cancer. Chrissy was a graduate student then, she just got her PhD in March and she was interested in breast cancer. She began to look at Src kinase and how its levels and expression patterns correlated with different types of breast cancer. Src kinase is an enzyme, which is a protein that speeds up chemical reactions a million-fold. It remodels the cytoskeleton and the plasma membrane [of a cell].

[She] found that levels [of Src kinase] were highest in those breast cancer tissues that were the most aggressive and invasive. What she did was manipulate the expression of this protein by turning it off. And she found that cells didn’t invade as well, didn’t migrate as well and didn’t form finger-like projections, invadapodia, which help break down the barrier and facilitate the initial steps in cancer cell invasion. When cancer cells take up residence and continue to grow, forming metastasists, that’s what kills people.

Chrissy started to look at a drug, dasatinib, which is an FDA-approved drug for a form of leukemia called Chronic Myeloid Leukemia (CML). We found that [blocking] the Src kinases didn’t so much stop the cells from surviving, but it kind of got them to stop growing as quickly. But what it also did, and I think this is something that needs to be exploited, is that it did affect their ability to migrate, to invade and to form those finger-like projections of invadapodia.

Q)   How can readers imagine this for themselves?
A)   You can think of it like a car. A car needs to move and the way it moves is turning on the engine and running on the four tires. So the idea is to knock out all the tires so our cancer car won’t move. If you can shoot out the tires of the car with a drug like dasatinib, then you’re going to slow down the cancer cell and extend peoples’ lives.

Q)   Is dasatinib something someone who currently has breast cancer can ask her doctor about?
A)   One goal is to make the disease go away, but an alternative goal is to have stable disease in check. If you can’t cure somebody of a cancer, you can make it a chronic disease. I think most people could live with that. The question is how to incorporate dasatinib into a multi-drug regimen as a second-line or third-line therapy for women with refractory, or relapsed, breast cancer.

New view: May Griffith holds up a biosynthetic replacement cornea.
Credit: Ottawa Hospital Research Institute



The results of a two-year study are as good as those achieved with donor corneas.

MIT Technology Review, August 30, 2010, by Nora Schultz

Patients with impaired vision because of a damaged cornea could soon regain their sight without need of a human donor transplant. Instead, such patients could be aided by an artificial but biosynthetic implant. One such implant has now been tested in patients over two years, and the results are as good as, or even better than, those achieved with donor corneas.

The transparent tissue that covers the surface of the eyes, the cornea, can be damaged by injury, infection, or inflammation, causing the eye to lose much of its ability to refract light and focus images on the retina. Such damage has caused loss of vision in millions of people around the world. The best treatment for cornea damage remains a transplant, but donor corneas are in chronically short supply.

Plastic replacements have been available for decades, but their implantation is still plagued by side effects such as infection and glaucoma. “They remain a last resort option for patients where all other options have failed, including donor transplants,” says Joachim Storsberg at the Fraunhofer Institute for Applied Polymer Research in Potsdam, Germany. Storsberg is developing plastic implants but was not involved with the current work.

Several other research groups are working on artificial corneas made from materials that encourage cell growth and are less likely to be rejected. But this is the first time the long-term effectiveness of such an implant has been tested in humans.

May Griffith of Linköping University in Sweden and Ottawa Hospital Research Institute, along with colleagues, developed the implant for patients with damage to only the top layers of the cornea. A partner company, Fibrogen, engineered yeast cells to manufacture the human protein collagen. The team then chemically cross-linked this collagen and let it harden in a mold in the shape of corneas, which they then implanted in place of the damaged cornea layers of 10 patients.

Although the implants do not contain any live cells, they mimic the flexible scaffold material that makes up the bulk of the stroma, the thickest layer of the cornea, which is essentially a natural hydrogel consisting mostly of collagen.

“Although donor corneas remain the gold standard, Griffith’s approach looks like it’s a close second, and very promising, at least if you don’t have persistent infections that destroy the regenerating tissue,” says Storsberg.

Griffith’s team reports this week in the journal Science Translational Medicine that two years after implantation, cells had repopulated the implants, and the outermost epithelial cell layer, which protects the eye from infection, had grown back over the implant in all patients. Vision in all ten patients improved to levels comparable to that of patients who have received donor corneas–but only when those ten patients also wore contact lens. “This is because stitches on the implants introduced bumps that impaired vision and need to be smoothed by contact lenses,” says Griffith. But using different suturing methods or replacing the stitches by gluing the implants to the eye with tissue adhesives could solve this problem, she argues, adding that the team has had encouraging results testing such alternatives in preliminary follow-up work.

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The team also observed regenerating nerves in all the corneas, and in nine out of 10 patients, the nerves grew all the way to the center of the implant, a result Griffith is particularly excited about. “The nerves are really important for the long-term health of the rest of the cornea–but regeneration does not happen reliably even in donor corneas,” she says. Her long-term expectation is that the implant will slowly degrade and be completely replaced by the natural scaffold regenerated by the cells that have repopulated the cornea.

Christopher Ta, an associate professor at Stanford University who’s working on another kind of hydrogel substitute for donor corneas, is also optimistic about Griffith’s work, which he says “has the potential to revolutionize the field of cornea transplantation. It is possible to see widespread use of this type of engineered cornea in the next five years.”

Desktop Cancer Check

By TR Editors

Photo Credit: Christopher Harting

MIT Technology Review, September/October 2010

A device that analyzes blood levels of prostate-specific antigen (PSA) is one of the first doctor’s-office uses of microfluidics–technology that can manipulate fluids on a chip at microscopic scales. When a cartridge bearing a blood sample is inserted into the tabletop device, an accurate reading can be completed in 15 minutes, helping monitor the health of patients with prostate cancer. The procedure used now involves sending a sample to a lab for analysis, which often takes a day or two. The device received European approval in June.

A Methicillin-resistant Staphylococcus Aureus (MRSA) bacteria strain is seen in a petri dish at a microbiological laboratory in Berlin, in this March 2008 file photo. Some British patients who underwent plastic surgery in South Asia now carry a new gene that has the potential to turn bacteria into the latest antibiotic resistant superbug, such as MRSA, according to an article published Wednesday in the journal Lancet Infectious Diseases.     Credit:  (Fabrizio Bensch/Reuters), August 30, 2010  —  Austria’s health ministry is reporting two cases of a new gene that allows bacteria to become a superbug.

The ministry says experts at the medical university in the southern city of Graz detected the gene, known as NDM-1, in two people, both of whom are believed to have been infected in hospitals abroad.

A statement Friday said a person from Pakistan was released in good health from Graz’s university clinic last year after successful treatment. It said another person from Kosovo is still under medical supervision there.

Researchers say the gene – which appears to be circulating widely in India – alters bacteria, making them resistant to nearly all known antibiotics.

Superbugs: ‘Slow Motion Doom and Gloom,’ Experts Says

The overuse of antibiotics has contributed to the increase in antibiotic resistant bugs. Over time, bacteria grow stronger than the treatments they may be regularly exposed to. And, according to many experts, there’s no end in sight.

“It’s slow motion doom and gloom,” say the experts. “We are feeling the limited availability of active antibiotics, and we’re put in situations where we don’t have active therapies to treat cases.”

Although researchers are not able to reverse the superbug genes, it is possible to slow the spread of superbugs, according to Dr. William Schaffner, chairman of preventive medicine at Vanderbilt University Medical Center.

“Antibiotics are used when they don’t have to be used, and are continued for too long,” said Schaffner.