Brain Cancer Treatment Using Genetic Material from Bone Marrow Cells

In a first-of-its-kind experiment using microvesicles generated from mesenchymal bone marrow cells (MSCs) to treat cancer, neurological researchers at Henry Ford Hospital have discovered a novel approach for treatment of tumors.

Specifically, the research team found that introducing genetic material produced by MSCs significantly reduced a particularly resistant form of malignant brain tumor in living lab rats.

“This is the first foray of its type in experimental cancer therapy, and it represents a highly novel and potentially effective treatment,” says Michael Chopp, Ph.D., scientific director of the Henry Ford Neuroscience Institute and vice chairman of the Department of Neurology at Henry Ford Hospital.

The research is published in the current issue Cancer Letters.

“I think this is an important and very novel approach for the treatment of cancers, and in this particular case the treatment of glioma,” says Dr. Chopp. “We have been at the forefront of developing microRNAs as a means to treat disease, such as cancer and neurological injury.

“This study shows it is effective in the living brain, and may even lend itself to specific cancer therapy, customized for the individual patient,” Chopp adds.

Chopp and his colleagues focused their efforts on glioma, by far the most common type of malignant brain tumor and one with a notably poor prognosis for survival.

Tumor cells were surgically implanted in the brains of anesthetized male lab rats and allowed to grow for five days.

The tumors then were injected with exosomes containing molecules of a microRNA called miR-146b – found in earlier Henry Ford research to have a strong effect on glioma cells.

Exosomes are microscopic “lipid bubbles” that once were thought to carry and get rid of “old” proteins that were no longer needed by the body. After they were more recently found to also carry RNA, whole new fields of study were suggested, including groundbreaking work by Henry Ford researchers.

In the rat study, Dr. Chopp and his colleagues used MSC bone marrow cells to produce the exosomes containing the miR-146b they injected into the cancerous tumors.

Five days after this treatment, the rats were euthanized and their brains were removed, prepared for study and examined. Tumor size was measured using computer software.

“We found that one injection of exosomes containing miR-146b five days after tumor implantation led to a significant reduction in tumor volume at 10 days after implant,” Chopp says. “Our data suggest that miR-146b elicits an anti-tumor effect in the rat brain, and that MSCs can be used as a ‘factory’ to generate exosomes genetically altered to contain miR-146b to effectively treat tumor.”

(Image: iStock)

Personalized Brain Mapping Technique Preserves Function Following Brain Tumor Surgery

Neurosurgeons can visualize important pathways in the brain using an imaging technique called diffusion tensor imaging (DTI), to better adapt brain tumor surgeries and preserve language, visual and motor function while removing cancerous tissue. In the latest issue of Neurosurgical Focus, researchers from the Perelman School of Medicine at the University of Pennsylvania review research showing that this ability to visualize relevant white matter tracts during glioma resection surgeries can improve accuracy and, in some groups, significantly extend survival (median survival of 21.2 months) compared to cases where DTI was not used  (median survival of 14 months).

"We can view the brain from the inside out now, with 3D images detailing connectivity within the brain, making a virtual intraoperative map," said senior author Steven Brem, MD, professor of Neurosurgery, chief of the Division of Neurosurgical Oncology and co-director of the Penn Brain Tumor Center. "Penn is at the forefront of a major shift in the field - we now have such detail about each individual’s brain tumor - combining diffusion tensor imaging and advanced imaging with the entire personalized diagnostics analysis available for all brain tumor patients at Penn Medicine."

Diffusion tensor imaging (DTI) provides a rendering of axon pathways, by tracking water molecules in the brain as they travel in a direction parallel to axonal fibers, in a 3D model known as “the diffusion tensor.” The diffusion tensor directly represents the direction of water and indirectly represents the orientation of white matter fibers. The colorful images, captured as part of an 8 minute sequence during an MRI, show representations of clusters of axon fibers, where each color indicates a direction of travel, and offer a glimpse of the interwoven communication superhighways of the brain.

"The DTI images can be overlaid with structural and functional MRI images, providing a hybrid map showing topography layered with a road map," said Neurosurgery resident Kalil Abdullah, MD, lead author of the paper. "This rendering gives us increased clarity to visualize important white matter tracts in the brain and adapt our surgical approaches to each person’s case. Rather than focusing on solely taking the tumor out, we can avoid damage to healthy tissue and preserve important pathways responsible for speech, vision and motor function."

Relying heavily on the expertise of radiologists who process and analyze the DTI images, including Ronald L. Wolf, MD, PhD, associate professor of Radiology at Penn, the research on DTI is being translated into clinical practice to guide surgical procedures. Further research efforts are targeted at defining language deficits before surgery and following-up post-operatively to determine any changes or improvements following treatment based on the use of DTI.

Working collaboratively with colleagues in Penn’s departments of Neurosurgery, Neurology, Radiology, Radiation Oncology, Nursing, Pathology and Laboratory Medicine and the Abramson Cancer Center, the Penn Brain Tumor Center combines the latest imaging, biomarker and genetic tumor testing to provide a personalized treatment plan for all types of brain cancers. Brain tumors are among the first areas of interest for Penn’s Center for Personalized Diagnostics (CPD), a joint initiative by Penn Medicine’s Department of Pathology and Laboratory Medicine and the Abramson Cancer Center, which integrates Molecular Genetics, Pathology Informatics, and Genomic Pathology for individualized patient diagnoses and to elucidate cancer treatment options for physicians.

(Image: Swedish Research)

Brain tumour cells killed by anti-nausea drug

New research from the University of Adelaide has shown for the first time that the growth of brain tumours can be halted by a drug currently being used to help patients recover from the side effects of chemotherapy.

The discovery has been made during a study looking at the relationship between brain tumours and a peptide associated with inflammation in the brain, called “substance P”.

Substance P is commonly released throughout the body by the nervous system, and contributes to tissue swelling following injury. In the brain, levels of substance P greatly increase after traumatic brain injury and stroke.

"Researchers have known for some time that levels of substance P are also greatly increased in different tumour types around the body," says Dr Elizabeth Harford-Wright, a postdoctoral fellow in the University’s Adelaide Centre for Neuroscience Research.

"We wanted to know if these elevated levels of the peptide were also present in brain tumour cells, and if so, whether or not they were affecting tumour growth. Importantly, we wanted to see if we could stop tumour growth by blocking substance P."

Dr Harford-Wright found that levels of substance P were greatly increased in brain tumour tissue.

Knowing that substance P binds to a receptor called NK1, Dr Harford-Wright used an antagonist drug called Emend® to stop substance P binding to the receptor. Emend® is already used in cancer clinics to help patients with chemotherapy-induced nausea.

The results were startling.

"We were successful in blocking substance P from binding to the NK1 receptor, which resulted in a reduction in brain tumour growth - and it also caused cell death in the tumour cells," Dr Harford-Wright says.

"So preventing the actions of substance P from carrying out its role in brain tumours actually halted the growth of brain cancer.

"This is a very exciting result, and it offers further opportunities to study possible brain tumour treatments over the coming years."

A*STAR scientists have identified a biomarker of the most lethal form of brain tumours in adults − glioblastoma multiforme. The scientists found that by targeting this biomarker and depleting it with a potential drug, they were able to prevent the progression and relapse of the brain tumour.

Brain satnav helps surgeons travel to a tumour

SATNAV is good at finding the easiest route to where you want to go. Now a version for the brain could allow a flexible probe to take the safest route to reach deep tissue. Together, the algorithm and probe could provide access to brain tumours that were previously deemed inoperable.

When surgeons want to take a biopsy from deep inside the brain, they face a problem - how to get there without damaging the brain tissue en route. Flexible needles are one solution. Ferdinando Rodriguez y Baena at Imperial College London and colleagues created such a probe in 2009, basing the design on the needle-like ovipositor that female wasps use to deposit eggs inside trees.

Just like the wasp’s ovipositor, the probe has a number of interlocking flexible shafts, each of which can slide independently of the others. The probe naturally sticks to the soft brain tissue, providing traction, which means that when one of the shafts slides further into the tissue the probe will flex. By controlling the relative movement of each shaft it is possible to send the probe snaking along a path through the tissue.

Rodriguez y Baena’s team has now begun to think about exactly which paths are best to take. “Some areas of the brain are more important than others and we needed a way to decide what route caused the least amount of damage to vital areas,” says team member Seong Young Ko at Chonnam National University in Gwangju, South Korea. “You would want to stay well away from major blood vessels and sensory areas, for example.”

The team has now developed an algorithm to direct the probe around these obstacles. It considers three factors: the distance from the scalp to the desired brain tissue, the proximity of the route to vital areas such as blood vessels or nerve bundles, and the accumulated risk along the way.

There is controversy over how to rate the importance of different parts of the brain, so the team tested the algorithm by giving arbitrary levels of importance to different areas. It revealed the path which should theoretically bring the least risk to a patient. Ko presented the algorithm at the BioRob 2012 conference in Rome, Italy, last month.

"The ability to take a curved path through the brain, selecting the most forgiving route to avoid critical regions, represents an intriguing breakthrough," says Katrina Firlik, a neurosurgeon in Greenwich, Connecticut, who was not involved in the research. "It could not only enhance safety but might even expand the surgical repertoire to include cases currently deemed inoperable."

That is the hope, says Ko. So far the probe has only been tested in animal tissue, but he says the goal is to use the algorithm to guide the safe implantation of electrodes deep in the brain and to improve the safety of taking biopsies from hard-to-reach tumours.