Brain Stem Cells Against Cancer?

Gliomas are a group of brain tumors where the most common type is also the most aggressive one. Chemotherapy and radiation have little effect on malignant gliomas, and patients survive only about a year after being diagnosed. But research at Lund University in Sweden provides hope that it may be possible in the future to develop stem cells from the brain into a new way to treat gliomas.

Neural stem cells have been shown to have the ability to recognize signals from tumor cells in the brain and migrate there. If stem cells are injected into a part of the brain in laboratory animals with a glioma in another part of their brain, the stem cells migrate over to the tumor area.

This has spawned the idea of having stem cells transport drugs or immune stimulants to the tumor. This was the principle the Lund scientists wanted to test. But as it turned out, no extra assistance was needed: the stem cells themselves had the ability to combat the tumor.

"We were truly amazed when we saw this effect! To be sure about the phenomenon, we ran several experiments with other stem cells, and it was confirmed that certain neural stem cells actually have an anti-tumor effect," says Karin Staflin. She is describing the findings in her dissertation, which she will soon defend.

It is as yet unknown just why this happens. One plausible reason is that both normal neural stem cells and glioma cells are immature, not fully mature cells. They are therefore more like each other than any other types of cells in the brain, which may enable them to 'speak' to each other and influence each other. The research team at Lund has also shown that stem cells can cure colon cancer in lab animals.

"Cells in aggressive malignant cancer forms are often characterized as being more immature than their environment. This may be what enables neural stem cells to affect intestinal cancer cells," says Karin Staflin.

Many years of research remain before the newly discovered principle is ready to be tested on humans. First, researchers need to learn to understand the mechanisms better and identify the factors in neural cells which make them so effective. The notion is still new, but it does provide a glimmer of hope for a cure for a thus far incurable disease.

The dissertation is titled Neural progenitor cells in malignancy and injury of the brain: A Trojan horse for gliomas?

The Swedish Research Council

The Swedish Research Council bears national responsibility for developing the country's basic research towards attainment of a strong international position. The Council has three main tasks: research funding, science communication and research policy. Research is the foundation for the development of knowledge in society, and the basis of high-quality education. Research is also crucial as a means of enhancing welfare through economic, social and cultural development.

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Researchers Urge Monitoring Of Bone Health During Chemotherapy

In laboratory tests on mice, researchers found that a medication often used to reduce toxic side effects of chemotherapy induced bone loss and helped tumors grow in bone. So the researchers at Washington University School of Medicine in St. Louis are recommending increased awareness of bone health during cancer treatments.

The medication studied is a growth factor commonly used to help cancer patients recover healthy blood counts after chemotherapy, which can destroy white blood cells. Low levels of white blood cells leave patients susceptible to infection.

"This growth factor encourages bone breakdown, and any therapy that decreases bone density could potentially enhance tumor growth in bone," says senior author Katherine Weilbaecher, M.D., assistant professor of medicine and of cell biology and physiology. "But there are things that can be done to counteract this. Physicians should carefully monitor their cancer patient's bone health with regular bone density scans (DEXA) and prescribe medications to prevent bone loss when needed. And patients should consume enough calcium and vitamin D and get sufficient exercise to maintain strong bones."

Weilbaecher and her colleagues found that when they gave mice an eight-day course of the growth factor, called granulocyte colony-stimulating factor (G-CSF), the mice lost bone mass and experienced increased bone tumor growth when injected with cancer cells. Their study will appear in an upcoming issue of the journal Blood and is now available online.

G-CSF is known by the trade names Neupogen, Neulasta and Granocyte. Clinical use of G-CSF has recently increased because by speeding blood cell regrowth it allows patients to undergo more intensive chemotherapy regimens in which anticancer agents are given at more frequent intervals. Studies have suggested these dose-dense therapies could prolong survival in women with breast cancer.

"We are not at all advocating ending G-CSF use," says Weilbaecher, an oncologist with the Siteman Cancer Center at Washington University School of Medicine and Barnes-Jewish Hospital. "G-CSF seems to have significant benefits for some cancer patients."

Although G-CSF had a strong effect on bone metastasis in the experimental mice, early clinical trials in humans using G-CSF with chemotherapy have so far shown no adverse effects on survival and no increase in bone metastasis. In fact, breast-cancer patients undergoing dose-dense chemotherapy with G-CSF support tend to have a longer disease-free period than those getting standard dosing without G-CSF.

"It's possible that women on G-CSF-supported chemotherapy could do even better if we paid more attention to skeletal health," says lead author Angela Hirbe, an M.D./Ph.D. student in Weilbaecher's lab. "Strengthening the skeleton would not only help prevent osteoporosis and fractures but also might give patients a survival advantage."

In the laboratory mice studied, G-CSF increased the number and activity of bone cells called osteoclasts, which resorb bone material as part of the normal process of bone turnover. The resulting loss of bone density created a favorable environment for bone tumor growth.

When the researchers injected melanoma or breast cancer cells into mice, those getting G-CSF developed a two-fold increase in tumor burden, a measure of the size and severity of tumors, compared to those that did not receive G-CSF.

Interestingly, mice treated with a bisphosphonate, an anti-osteoporosis agent that inhibits osteoclasts, were resistant to the effects of G-CSF on bone tumor growth. Weilbaecher is currently investigating bisphosphonates as a means to prevent tumor metastasis to bone in breast cancer patients.

"We used G-CSF as a tool to understand the implications for tumor growth when osteoclast activity is revved up," Weilbaecher says. "But G-CSF isn't unique in its effect. For example, antihormone therapies used to treat breast and prostate cancer also can decrease bone mineral density. We would like to see clinical trials instigated to study the effects of such cancer therapies on bone health and tumor metastasis."

Hirbe AC, Uluçkan -, Morgan EA, Eagleton MC, Prior JL, Piwnica-Worms D, Trinkaus K, Apicelli A, Weilbaecher K. Granulocyte colony-stimulating factor enhances bone tumor growth in mice in an osteoclast-dependent manner. Blood Dec 27, 2006 (advance online publication).

Funding from the National Cancer Institute supported this research.

Washington University School of Medicine's full-time and volunteer faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Children's hospitals. The School of Medicine is one of the leading medical research, teaching and patient care institutions in the nation, currently ranked fourth in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Children's hospitals, the School of Medicine is linked to BJC HealthCare. Siteman Cancer Center is the only NCI-designated Comprehensive Cancer Center within a 240-mile radius of St. Louis. Siteman Cancer Center is composed of the combined cancer research and treatment programs of Barnes-Jewish Hospital and Washington University School of Medicine.

Washington University in St. Louis
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High-Power MRI Helps Surgical Team Predict Outcomes In Unusual Tumor Cases

A Mayo Clinic surgical team has found that using a 3-Tesla MRI in surgical decision making provides a new level of capability to predict surgical outcomes that improves patient care by minimizing the potential for unsuccessful tumor-removal surgeries. The Mayo Clinic report appears in the December issue of the Journal of Neurosurgery.

In their report, Mayo physicians describe a case study of five patients. Four had neurofibromatosis, a condition with a predisposition to nerve-related tumors. All patients suffered from growths called "sciatic notch dumbbell-shaped" tumors. The tumors were benign, but resulted in neurologic dysfunction and disabling pain.

"In the past, if surgeons couldn't tell prior to surgery where the exact location of the large tumor was in relation to the sciatic nerve, it meant they couldn't predict in which cases surgery could be performed safely," explains Robert Spinner, M.D., the lead neurosurgeon on the Mayo Clinic team.

The team used an advanced magnetic resonance imaging (MRI) system performed on a 3-Tesla magnet to help identify suitable candidates for a difficult tumor-removal surgery. A Tesla is a unit of magnet strength. A 3-Tesla is one of the strongest commercially available.

Significance of the Mayo Clinic Case Study

A standardized surgical approach for safe and complete removal of sciatic notch dumbbell-shaped tumors has been problematic for at least three reasons. These tumors are:

-- relatively rare and therefore hard to study

-- anatomically difficult to reach and remove without injuring the main sciatic nerve

-- difficult to visualize before surgery with enough detail to distinguish tumor boundaries from nerve

The current Mayo Clinic report begins to change this situation by documenting a new multidisciplinary approach for obtaining the desired favorable surgical outcomes.

Surgeons need an accurate picture of how and whether they can remove a tumor while protecting a nerve. Otherwise, patients may be exposed to the risks of surgery without achieving surgical benefits if the tumor is inoperable because complete removal would damage a nerve. "Our experience demonstrates the advantages of predictive imaging at the outset," says Dr. Spinner. "With an integrated team of surgeons from three specialties, and an experienced radiologist specializing in advanced peripheral nerve imaging using the 3-Tesla MRI, we have devised an approach that minimizes unsuccessful tumor-removal surgeries."

About the Study

With the 3-Tesla MRI images, Mayo Clinic surgeons from three specialties -- neurosurgery, colorectal and orthopedic surgery -- obtained sufficiently detailed pictures of the tumor and nerve relationship before surgery in all five cases to accurately predict which patients would benefit from surgery. In three cases the tumor was predicted to be distinct from the main sciatic nerve, and the tumor was safely removed. All three patients experienced relief from pain and had no recurrent growth one year after surgery. In the other two cases, the tumor was predicted to be so entwined in the nerve that surgery would have damaged the nerve. Those patients did not undergo surgery.

Dr. Spinner said the team will continue to refine the approach to improve the care that these patients receive. "This new technology allows a multidisciplinary approach to be performed safely in these rare tumors that were once considered unresectable," he says. "In addition, the same techniques that we have developed have tremendous applications to many patients who have peripheral nerve tumors in more common locations."

Collaboration

Other members of the Mayo Clinic team included: Toshiki Endo, M.D.; Kimberly Amrami, M.D.; Eric Dozois, M.D.; Dusica Babovic-Vuksanovic, M.D.; and Franklin Sim, M.D.

Mayo Clinic
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Blog Carnival Edit

Cancer blogs carnival

Vahid Chaychi presents Coping with Depression When You Have Cancer posted at Cancer and Health Topics.

Andrea Dickson presents The Cost of Tanning posted at Wise Bread - Living large on a small budget.

Vahid Chaychi presents HPV (cause of cervical cancer) Vaccine Causes Controversy posted at Healthoma.com.

See the top online resources for prostate... posted at Prostate cancer treatment

Newly Released Prisoners At High Risk For Death

Prisoners who have been recently released from prison have a high death rate, especially in the first two weeks after release, a new study finds. The findings will be published in the Jan. 11 issue of The New England Journal of Medicine.

The study was conducted by Ingrid Binswanger, MD, of the University of Colorado at Denver and Health Sciences Center's School of Medicine, Marc Stern, MD, health services director of the Washington State Department of Corrections, and other researchers at the University of Washington and Harborview Medical Center in Seattle. Binswanger conducted the research while taking part in the Robert Wood Johnson Clinical Scholars Program at the University of Washington and the VA Puget Sound Health Care System.

In the first study of its kind in the U.S., Binswanger analyzed data from 30,237 inmates released from prison between 1999 and 2003 in Washington state. The sample represented almost all prisoners released during that time. Of those individuals, 443 died during an average follow-up time of 1.9 years.

The death rates of the released prisoners were compared to the death rates of other Washington residents of the same age, gender, and race. The study found that newly released prisoners were 12.7 times as likely to die in the two weeks following their release compared to other state residents in the same demographic groups. Over the whole study, the former inmates were 3.5 times more likely to die than other state residents. The death rate among former inmates was considerably higher than the death rate among inmates in prison.

"These striking findings suggest that former inmates are at high risk for death following their release from prison," said Binswanger. "These results, along with findings from studies done in other countries, underscore the need for novel programs to reduce the risk of death in former inmates."

The leading causes of death were drug overdose, cardiovascular disease, homicide and suicide. Nearly one quarter of the deaths were a result of drug overdose, and half of these deaths resulted from cocaine. After cocaine, most overdose deaths were caused by methamphetamine and opiates like heroin. Lung cancer represented half of all the cancer deaths in this population.

Younger individuals tended to die from overdose, homicide and suicide, whereas older individuals tended to die from cardiovascular disease and cancer. Binswanger recommends programs targeted by age to address this difference.

"The U.S. has exceptionally high rates of incarceration," said Binswanger. "When a released prisoner dies, it may have an impact beyond his own life, affecting families and communities. These findings suggest that we need programs and policies targeted at decreasing the risk of death as former inmates transition back into their communities."

Binswanger is a physician researcher and an assistant professor in the Division of General Internal Medicine at UCDHSC's School of Medicine. Her research focuses on health, the criminal justice system, and vulnerable populations.

The School of Medicine faculty work to advance science and improve care as the physicians, educators and scientists at University of Colorado Hospital, The Children's Hospital, Denver Health, National Jewish Medical and Research Center and the Veterans Administration Medical Center. The School is part of the University of Colorado at Denver and Health Sciences Center, one of three universities in the University of Colorado system. For more information, visit the Web site at http://www.uchsc.edu or the UCDHSC Newsroom at http://www.uchsc.edu/news.

University of Colorado at Denver and Health Sciences Center
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http://www.uchsc.edu/