Charles Eberhart, M.D., Ph.D. Johns Hopkins scientists have published laboratory data refuting studies that suggest blood vessels that form within brain cancers are largely made up of cancer cells. The theory of cancer-based blood vessels calls into question the use and value of anticancer drugs that target these blood vessels, including bevacizumab (Avastin).
‘We don’t question whether brain cancer cells have the potential to express blood vessel markers and may occasionally find their way into blood vessels, but we do question the extent to which this happens,’ says Charles Eberhart, M.D., Ph.D., chief of neuropathology at the Johns Hopkins University School of Medicine. ‘In general, we find no evidence in our study that these vessels contain substantial amounts of cancer cells.’
Eberhart, professor of pathology, ophthalmology and oncology at Johns Hopkins, said he first encountered claims about the cancerous nature of tumour blood vessels about a year ago when he was invited to join students at a journal club meeting, a forum for discussing studies published in medical journals. ‘My first reaction to this research was ‘How could this be true?’’ says Eberhart. ‘Our clinical experience examining tissue from brain cancers does not support it.’
Studies have long demonstrated that malignant brain tumours contain large numbers of blood vessels to feed their growing demand for nutrients. The blood vessels are formed when tumours pump out growth factors that increase vessel production. Such studies opened the door to treatment strategies that specifically targeted blood-vessel growth and the vessel cells themselves.
More recently, scientists in Italy and the Memorial Sloan Kettering Cancer Center in New York published results of studies suggesting that these tumour blood vessels are made by primitive types of brain cancer cells that are a form of stem cells. In their studies, they found tumour markers on blood vessel cells in 20 to 90 percent of their brain cancer samples. The U.S./Italian research teams said their findings also suggested that the cancer-like blood vessels were more prone to drug resistance, potentially explaining why drugs like bevacizumab yield tumour-shrinking responses, but only for short periods. Bevacizumab is currently approved by the U.S. Food and Drug Administration for use in patients with colorectal, lung, kidney and brain cancers.
Eberhart said pathologists, including those who work on brain tissue, use certain tissue-based techniques to distinguish cancer cells from normal ones. When evaluating specimens of brain tissue removed during surgery for suspected cancer, he said, most pathologists agree that blood vessel cells in these specimens consistently lack the molecular changes associated with cancer cells, according to Eberhart. In fact, they often use these blood vessel cells as ‘normal controls’ to compare with potentially cancerous ones.
After the journal club experience, Eberhart teamed up with fellow neuropathologist Fausto Rodriguez, M.D., and colleagues at the Dana Farber Cancer Institute and Harvard Medical School in Boston to look more closely at the molecular features of blood vessel cells in brain cancer samples. They tested more than 100 samples from patients at Johns Hopkins and Dana Farber for EGFR and IDH1 markers, two common genes altered in brain cancer.
‘We also used a marker called CD34 to differentiate vascular [blood vessel] cells from other types of cells,’ says Rodriguez, assistant professor of pathology at Johns Hopkins. The research teams found no more than 10 percent of their samples contained vascular cells with EGFR or IDH1 cancer markers, and in those rare tumour samples, only a few cells exhibited those markers. The Johns Hopkins-Dana Farber-Harvard team tested all parts of the vessel walls for presence of the cancer markers.
Although the two groups used different markers to identify vessel cells, Rodriguez says ‘there is no marker that is absolute for each cell.’ Johns Hopkins Medical Institutions

By simply shining a tiny light within the small intestine, close to that organ’s junction with the pancreas, physicians at Mayo Clinic’s campus in Florida have been able to detect pancreatic cancer 100 percent of the time in a small study. The light, attached to a probe, measures changes in cells and blood vessels in the small intestine produced by a growing cancer in the adjoining pancreas.
This minimally invasive technique, called Polarisation Gating Spectroscopy, will now be tested in a much larger international clinical trial led by the Mayo Clinic researchers. The preliminary study suggests it may be possible, one day, to use a less invasive endoscope to screen patients for early development of pancreatic cancer.
The pancreas is notoriously hard to reach and see due to its very deep location in the abdomen, surrounded by intestines. The study investigators theorised that there may be changes in the nearby ‘normal appearing’ tissue of the small intestine which is much more accessible.
‘No one ever thought you could detect pancreatic cancer in an area that is somewhat remote from the pancreas, but this study suggests it may be possible,’ says Dr. Wallace, the chairman of the Division of Gastroenterology at Mayo Clinic in Florida. ‘Although results are still preliminary, the concept of detection field effects of nearby cancers holds great promise for possible early detection of pancreatic cancer.’
Pancreatic cancer is one of the most deadly of human tumours. It is only curable in 5 percent of cases, and even when it is surgically removed, 70 percent of patients have a recurrence that is fatal, Dr. Wallace says. There are no ways currently to detect the cancer early enough to cure a substantial number of patients, he says.
Pancreatic cancer is now usually detected through an imaging scan, followed by an invasive biopsy. Tumours found in this way are usually at an advanced stage.
In this study, the Mayo Clinic physicians tested a light probe developed by their long-time collaborators at Northwestern University.
The light, attached to a small fibre-optic probe known as an endoscope, measures the amount of oxygenated blood as well as the size of blood vessels in tissue near the duct where the pancreas joins the small intestine. Because a growing tumour requires a heightened supply of blood, normal tissue in the vicinity of the cancer Mayo Clinic Arizona

Beckman Coulter, Inc. has obtained a CLIA Certificate of Registration, along with Massachusetts State Licensure, allowing Beckman Coulter Genomics to begin accepting clinical samples for genetic sequencing – the most technically complex CLIA category – and to provide those results to physicians for their use in treating, diagnosing and preventing disease in patients.

This milestone certification paves the way for detection of BRAF exon 11 (codons 439-477) and exon 15 (codons 581-620) for mutations using PCR-based DNA Sanger sequencing, the first clinical molecular diagnostic assay the company has developed. Plans call for Beckman Coulter Genomics to develop further CLIA-certified assays using next-generation sequencing for a number of oncology and infectious disease applications.

‘This certification allows Beckman Coulter to work more closely with physicians to bring the promise of high-quality molecular diagnostics to benefit greater numbers of patients,’ said Joseph Repp, vice president and general manager of Beckman Coulter Genomics. ‘We’re actively working to bring additional assays to physicians and clinical researchers across the country, as well as help all our customers further their understanding of genetic involvement in disease states.’

Researchers from the Perelman School of Medicine at the University of Pennsylvania have identified an abnormal amount a protein called Prostaglandin D2 in the bald scalp of men with male pattern baldness, a discovery that may lead directly to new treatments for the most common cause of hair loss in men. In both human and animal models, researchers found that a prostaglandin known as PGD2 and its derivative, 15-dPGJ2, inhibit hair growth. The PGD2-related inhibition occurred through a receptor called GPR44, which is a promising therapeutic target for androgenetic alopecia in both men and women with hair loss and thinning.
Male pattern baldness strikes 8 of 10 men under 70 years old, and causes hair follicles to shrink and produce microscopic hairs, which grow for a shorter duration of time than normal follicles.
Researchers took an unbiased approach when scanning for potential biological causes of baldness, looking in scalp tissue from balding and non-bald spots from men with male pattern baldness and then corroborating findings in mouse models. They found that levels of PGD2 were elevated in bald scalp tissue at levels 3 times greater than what was found in comparative haired scalp of men with androgenetic alopecia. When PGD2 was added to cultured hair follicles, PGD2-treated hair was significantly shortened, while PGD2’s derivative, 15-dPGJ2, completely inhibited hair growth.
‘Although a different prostaglandin was known to increase hair growth, our findings were unexpected, as prostaglandins haven’t been thought about in relation to hair loss, yet it made sense that there was an inhibitor of hair growth, based on our earlier work looking at hair follicle stem cells,’ said George Cotsarelis, MD, chair and professor of Dermatology, and senior author on the studies. In a Penn study published in the Journal of Clinical Investigation last year, underlying hair follicle stem cells were found intact, suggesting that the scalp was lacking an activator or something was inhibiting hair follicle growth.
Prostaglandins are well characterised for their role in many bodily functions — controlling cell growth, constricting and dilating smooth muscle tissue — and a different prostaglandin (F2alpha) is known to increase hair growth. Researchers found that as PGD2 inhibits hair growth, other prostaglandins work in opposition, enhancing and regulating the speed of hair growth.
While these studies looked at AGA in men, the researchers noted that prostaglandins may represent a common pathway shared by both men and women with AGA. Future studies, potentially testing topical treatments that may target GPR44, can determine whether targeting prostaglandins will benefit woman with AGA as well. Penn University

Mayo Clinic researchers have identified an immune system deficiency whose presence shows someone is up to four times likelier to die than a person without it. The glitch involves an antibody molecule called a free light chain; people whose immune systems produce too much of the molecule are far more likely to die of a life-threatening illness such as cancer, diabetes and cardiac and respiratory disease than those whose bodies make normal levels.
Researchers studied blood samples from nearly 16,000 people 50 and older enrolled in a population-based study of plasma cell disorders in Olmsted County, Minn. They found that those who had the highest level of free light chains — the top 10 percent — were about four times more at risk of dying than those with lower levels. Even after accounting for differences in age, gender and kidney function, the risk of death was roughly twice as high.
The study suggests that high levels of free light chains are markers of increased immune system response to infection, inflammation or some other serious disorders, says lead researcher Vincent Rajkumar, M.D., a Mayo Clinic hematologist.
Researchers have known that high levels of free light chains are associated with increased risk of death among patients with plasma disorders, such as lymphomas and other blood cancers, but this is the first study to find that high levels of light chains are associated with increased mortality in the general population. Free light chain levels can be measured by using a serum free light chain assay, a simple blood test. This test is often used to monitor light chain levels in patients with plasma disorders such as myeloma to gauge how well they are responding to treatment.
However, Dr. Rajkumar cautions against administering this test with the intent of gauging one’s risk of death.
‘We do not recommend this test as a screening test, because it will only cause alarm,’ Dr. Rajkumar says. ‘We do not know why this marker is associated with higher rates of death. We do not have a way of turning things around. Therefore, I would urge caution in using this test until we figure out what to do about it and what these results mean.’ Mayo Clinic Minnesota