Posts tagged tumor

Researchers from Plymouth University Peninsula Schools of Medicine and Dentistry are part of an international team which has for the first time identified the role of a tumour suppressor in peripheral neuropathy in those suffering multiple tumours of the brain and nervous system.

One in 25,000 people worldwide is affected by neurofibromatosis type 2 (NF2), a condition where the loss of a tumour suppressor called Merlin results in multiple tumours in the brain and nervous system.

Sufferers may experience 20 to 30 tumours at any one time and such numbers often lead to hearing loss, disability and eventually death. Those with NF2 may also experience peripheral neuropathy, which is when the nerves carrying messages to and from the brain and spinal column to the rest of the body do not work.

Peripheral neuropathy leads to further complications for NF2 sufferers, such as pain and numbness, muscle problems, problems with body organs and other symptoms of nerve damage, such as bladder problems, uncontrollable sweating and sexual dysfunction.

Researchers from Plymouth University Peninsula Schools of Medicine and Dentistry are part of an international research team which has for the first time identified the role of a tumour suppressor called Merlin in regulating the integrity of axons. Axons are nerve fibres which transmit information around the body and it is these are that damaged in peripheral neuropathy.

The research team showed that Merlin regulates a protein called neurofilament which supplies structural support for the axon. A better understanding of this mechanism could lead to effective drug therapies to alleviate the symptoms of peripheral neuropathy in patients with NF2.

The results of the research is published this week in Nature Neuroscience.

(Source: plymouth.ac.uk)

(Image Credit: Stanford University)

A team of brain cancer researchers at Barrow Neurological Institute at St. Joseph’s Hospital and Medical Center has effectively treated brain tumor cells using a unique combination of diet and radiation therapy. The study, “The Ketogenic Diet Is an Effective Adjuvant to Radiation Therapy for the Treatment of Malignant Glioma,” was published in PLOS ONE.

Led by Adrienne C. Scheck, PhD, Principal Investigator in Neuro-Oncology and Neurosurgery Research at Barrow, the groundbreaking research studied the effects of the ketogenic diet in conjunction with radiation therapy for the treatment of malignant gliomas, an aggressive and deadly type of brain tumor. The ketogenic diet is a high-fat, low-carbohydrate diet that alters metabolism and is used in the treatment of pediatric epilepsy that does not respond to conventional therapies. The diet’s affects on brain homeostasis have potential for the treatment of other neurological diseases, as well.

In the study, mice with high-level malignant gliomas were maintained on either a standard or a ketogenic diet. Both groups received radiation therapy. Dr. Scheck’s team discovered that animals fed a ketogenic diet had an increased median survival of approximately five days relative to animals maintained on a standard diet. Of the mice that were fed a ketogenic diet and received radiation, nine of 11 survived with no signs of tumor recurrence, even after being switched back to standard food, for over 200 days. None on the standard diet survived more than 33 days.

One theory behind the success of the treatment is that the ketogenic diet may reduce growth factor stimulation, inhibiting tumor growth. Barrow scientists also believe that it may reduce inflammation and edema surrounding the tumors. This is believed to be the first study of its kind to look at the effects of the ketogenic diet with radiation.

Dr. Scheck believes that the study has promising implications in the treatment of human malignant gliomas. “We found that the ketogenic diet significantly enhances the anti-tumor effect of radiation, which suggests that it may be useful as an adjuvant to the current standard of care for the treatment of human malignant gliomas,” she says.

Dr. Scheck adds that the ketogenic diet could quickly and easily be added into current brain tumor treatment plans as an adjuvant therapy without the need for FDA approval. She is currently exploring options for clinical trials.

(Source: eurekalert.org)

ScienceDaily (July 9, 2012) — Scientists showed in mice that disabling a gene linked to a common pediatric tumor disorder, neurofibromatosis type 1 (NF1), made stem cells from one part of the brain proliferate rapidly. But the same genetic deficit had no effect on stem cells from another brain region.

The results can be explained by differences in the way stem cells from these regions of the brain respond to cancer-causing genetic changes.

NF1 is among the world’s most common genetic disorders, occurring in about one of every 3,000 births. It causes a wide range of symptoms, including brain tumors, learning disabilities and attention deficits.

Brain tumors in children with NF1 typically arise in the optic nerve and do not necessarily require treatment. If optic gliomas keep growing, though, they can threaten the child’s vision. By learning more about the many factors that contribute to NF1 tumor formation, scientists hope to develop more effective treatments.

"To improve therapy, we need to develop better ways to identify and group tumors based not just on the way they look under the microscope, but also on innate properties of their stem cell progenitors," says David H. Gutmann, MD, PhD, the Donald O. Schnuck Family Professor of Neurology.

The study appears July 9 in Cancer Cell. Gutmann also is the director of the Washington University Neurofibromatosis Center.

In the new study, researchers compared brain stem cells from two primary sources: the third ventricle, located in the midbrain, and the nearby lateral ventricles. Before birth and for a time afterward, both of these areas in the brain are lined with growing stem cells.

First author Da Yong Lee, PhD, a postdoctoral research associate, showed that the cells lining both ventricles are true stem cells capable of becoming nerve and support cells (glia) in the brain. Next, she conducted a detailed analysis of gene expression in both stem cell types.

"There are night-and-day differences between these two groups of stem cells," Gutmann says. "These results show that stem cells are not the same everywhere in the brain, which has real consequences for human neurologic disease."

The third ventricle is close to the optic chiasm, the point where the optic nerves cross and optic gliomas develop in NF1 patients. Lee and Gutmann postulated that stem cells from this ventricle might be the source of progenitor cells that can become gliomas in children with NF1.

To test the theory, they disabled the Nf1 gene in neural stem cells from the third and lateral ventricles in the mice. This same gene is mutated in patients with NF1, increasing their risk of developing tumors.

Lee found that loss of Nf1 activity had little effect on stem cells from the lateral ventricle, but stem cells from the third ventricle began to divide rapidly, a change that puts them closer to becoming tumors.

The third ventricle usually stops supplying stem cells to the brain shortly after birth. When researchers inactivated the Nf1 gene before the third ventricle closed, the mice developed optic gliomas. When they waited until the third ventricle had closed to inactivate the Nf1 gene, gliomas did not develop.

Gutmann plans further studies to determine whether all NF1-related optic gliomas form in cells descended from the third ventricle. He suspects that additional factors are necessary for optic gliomas to form in cooperation with Nf1 gene loss in third-ventricle stem cells.

"We have to recognize that cancers which appear very similar actually represent a collection of quite different diseases," he says. "Tumors are like us — they’re defined by where they live, what their families are like, the traumas they experience growing up, and a variety of other factors. If we can better understand the interplay of these factors, we’ll be able to develop treatments that are much more likely to succeed, because they’ll target what is unique about a specific patient’s tumor."

Source: Science Daily

February 16th, 2012

Researchers have created a living 3-D model of a brain tumor and its surrounding blood vessels. In experiments, the scientists report that iron-oxide nanoparticles carrying the agent tumstatin were taken by blood vessels, meaning they should block blood vessel growth. The living-tissue model could be used to test the effectiveness of nanoparticles in fighting other diseases. Results appear in Theranostics.

Brown University scientists have created the first three-dimensional living tissue model, complete with surrounding blood vessels, to analyze the effectiveness of therapeutics to combat brain tumors. The 3-D model gives medical researchers more and better information than Petri dish tissue cultures.

The researchers created a glioma, or brain tumor, and the network of blood vessels that surrounds it. In a series of experiments, the team showed that iron-oxide nanoparticles ferrying the chemical tumstatin penetrated the blood vessels that sustain the tumor with oxygen and nutrients. The iron-oxide nanoparticles are important, because they are readily taken up by endothelial cells and can be tracked by magnetic resonance imaging.

Previous experiments have shown that tumstatin was effective at blocking endothelial cell growth in gliomas. The tests by the Brown researchers took it to another level by confirming, in a 3-D, living environment, the iron-oxide nanoparticles’ ability to reach blood vessels surrounding a glioma as well as tumstatin’s ability to penetrate endothelial cells.

“The 3-D glioma model that we have developed offers a facile process to test diffusion and penetration into a glioma that is covered by a blood vessel-like coating of endothelial cells,” said Don Ho, a graduate student in the lab of chemistry professor Shouheng Sun and the lead author of the paper in the journal Theranostics. “This assay would save time and money, while reducing tests in living organisms, to examine an agent’s 3-D characteristics such as the ability for targeting and diffusion.”

The tissue model concept comes from Jeffrey Morgan, a bioengineer at Brown and a corresponding author on the paper. Building on that work, Ho and others created an agarose hydrogel mold in which rat RG2-cell gliomas roughly 200 microns in diameter formed. The team used endothelial cells derived from cow respiratory vessels, which congregated around the tumor and created the blood vessel architecture. The advantage of a 3-D model rather than Petri-dish-type analyses is that the endothelial cells attach to the tumor, rather than being separated from the substrate. This means the researchers can study their formation and growth, as well as the action of anti-therapeutic agents, just as they would in a living organism.

“You want to see nanoparticles that diffuse through the endothelial cells, which is lost in 2-D because you just have diffusion into media,” Ho said.

Other 3-D tissue models have been “forced cell arrangements,” Ho said. The 3-D glioma model, in contrast, allowed the glioma and the endothelial cells to assemble naturally, just as they would in real life. “It more clearly mimics what would actually happen,” Ho explained.

The group then attached tumstatin, part of a naturally occurring protein found in collagen, to iron-oxide nanoparticles and dosed the mold. True to form, the nanoparticles were gobbled up by the endothelial cells. In a series of in vitro experiments, the team reported the tumstatin iron-oxide nanoparticles decreased vasculature growth 2.7 times more than under normal conditions over eight days. “The growth is pretty much flat,” Ho said. “There’s no new growth of endothelial cells.” The next step is to test the tumstatin nanoparticles’ performance in the 3-D environment.

“This model has significant potential to help in the testing and optimization of the design of therapeutic/diagnostic nanocarriers and determine their therapeutic capabilities,” the researchers write.

Source: Neuroscience News