Metabolic Protein Launches Sugar Feast That Nurtures Brain Tumors

Researchers at The University of Texas MD Anderson Cancer Center have tracked down a cancer-promoting protein’s pathway into the cell nucleus and discovered how, once there, it fires up a glucose metabolism pathway on which brain tumors thrive.

They also found a vital spot along the protein’s journey that can be attacked with a type of drug not yet deployed against glioblastoma multiforme, the most common and lethal form of brain cancer. Published online by Nature Cell Biology, the paper further illuminates the importance of pyruvate kinase M2 (PKM2) in cancer development and progression.

"PKM2 is very active during infancy, when you want rapid cell growth, and eventually it turns off. Tumor cells turn PKM2 back on - it’s overexpressed in many types of cancer," said Zhimin Lu, M.D., Ph.D., the paper’s senior author and an associate professor in MD Anderson’s Department of Neuro-Oncology.

Lu and colleagues showed earlier this year that PKM2 in the nucleus also activates a variety of genes involved in cell division. The latest paper shows how it triggers aerobic glycolysis, processing glucose into energy, also known as the Warburg effect, upon which many types of solid tumors rely to survive and grow.

"PKM2 must get to the nucleus to activate genes involved in cell proliferation and the Warburg effect," Lu said. "If we can keep it out of the nucleus, we can block both of those cancer-promoting pathways. PKM2 could be an Achilles’ heel for cancer."

By pinpointing the complicated steps necessary for PKM2 to penetrate the nucleus, Lu and colleagues found a potentially druggable target that could keep the protein locked in the cell’s cytoplasm.

(Image Credit: Wikimedia Commons)

For brain tumors, origins matter

Cancers arise when a normal cell acquires a mutation in a gene that regulates cellular growth or survival. But the particular cell this mutation happens in—the cell of origin—can have an enormous impact on the behavior of the tumor, and on the strategies used to treat it.

Robert Wechsler-Reya, Ph.D., professor and director of the Tumor Development Program in Sanford-Burnham’s NCI-designated Cancer Center, and his team study medulloblastoma, the most common malignant brain cancer in children. A few years ago, they made an important discovery: medulloblastoma can originate from one of two cell types: 1) stem cells, which can make all the different cell types in the brain or 2) neuronal progenitor cells, which can only make neurons.

Stem cells and progenitor cells are regulated by different growth factors. So, Wechsler-Reya thought, maybe the tumors arising from these cells respond differently to different therapies…

In a study published recently in the journal Oncogene, he and his team show that this is indeed the case. They looked at one growth factor in particular—basic fibroblast growth factor (bFGF)—and found that while it induces stem cell growth, it also inhibits neuronal progenitor cell growth.

What’s more, the researchers discovered that bFGF also blocks the growth of tumors that originate from progenitors. When they treated a mouse model of medulloblastoma with bFGF, it dramatically inhibited tumor growth.

Cat brain surgery: the story of an operation – in pictures

Harry, a 12-year-old maine coon, has a tumour on his pituitary gland, causing uncontrolled diabetes. In an attempt to save his life, his owners have opted for cutting-edge brain surgery at the Royal Veterinary College’s Queen Mother hospital for animals.

Scientists Identify New Stem Cells with Therapeutic Potential

The discovery, published in the journal PLOS Biology, offers new opportunities in the treatment of cardiovascular diseases, cancer and many other diseases.

The growth of new blood vessels – angiogenesis – occurs during the repair of damaged tissue and organs in adults. However, malignant tumors also grow new blood vessels in order to receive oxygen and nutrients. As such, angiogenesis is both beneficial and detrimental to health, depending on the context, requiring therapeutic approaches that can either help to stimulate or prevent it. Therapeutics that aim to prevent the growth of new blood vessels are already in use, but the results are often more modest than predicted.

For more than a decade, Prof Petri Salvén of the University of Helsinki and his colleagues have studied the mechanisms of angiogenesis to discover how blood vessel growth could be prevented or accelerated effectively.

“We succeeded in isolating endothelial cells with a high rate of division in the blood vessel walls of mice. We found these same cells in human blood vessels and blood vessels growing in malignant tumors in humans. These cells are known as vascular endothelial stem cells. In a cell culture, one such cell is capable of producing tens of millions of new blood vessel wall cells,” Prof Salvén said.

From their studies in mice, the team was able to show that the growth of new blood vessels weakens, and the growth of malignant tumors slows, if the amount of these cells is below normal. Conversely, new blood vessels form where these stem cells are implanted.

3D fetus fly-through peers inside abnormal bodies

Thanks to MRI techniques, you can see what a baby looks like before it’s born. But now these images can also be used to peer inside the body of a fetus, generating a fly-through of internal tissues that rivals the view you would get from a video.

Developed by Jorge Lopes from the National Institute of Technology (INT) in Rio de Janeiro, Brazil, and colleagues, the system can quickly produce a 3D virtual tour through a region of interest, usually to examine congenital anomalies. Using a combination of software, a doctor can produce a reconstruction after an MRI scan by selecting the camera angle and movement desired. In this video, a view into the lungs and airways of two unborn babies with tumours helped determine if their breathing would be affected after birth.

In addition to virtual models, the team can also produce 3D printed versions of an unborn child (see image above). According to Lopes, physical models can help describe a condition to expectant parents and illustrate surgical procedures required, as well as being useful for blind mothers to get a sense of their baby’s appearance.

Aggressive Brain Tumors Can Originate From a Range of Nervous System Cells

Scientists have long believed that glioblastoma multiforme (GBM), the most aggressive type of primary brain tumor, begins in glial cells that make up supportive tissue in the brain or in neural stem cells. In a paper published October 18 in Science, however, researchers at the Salk Institute for Biological Studies have found that the tumors can originate from other types of differentiated cells in the nervous system, including cortical neurons.

GBM is one of the most devastating brain tumors that can affect humans. Despite progress in genetic analysis and classification, the prognosis of these tumors remains poor, with most patients dying within one to two years of diagnosis. The Salk researcher’s findings offer an explanation for the recurrence of GBM following treatment and suggest potential new targets to treat these deadly brain tumors.

"One of the reasons for the lack of clinical advances in GBMs has been the insufficient understanding of the underlying mechanisms by which these tumors originate and progress," says Inder Verma, a professor in Salk’s Laboratory of Genetics and the Irwin and Joan Jacobs Chair in Exemplary Life Science.

To better understand this process, Verma’s team harnessed the power of modified viruses, called lentiviruses, to disable powerful tumor suppressor genes that regulate the growth of cells and inhibit the development of tumors. With these tumor suppressors deactivated, cancerous cells are given free rein to grow out of control.

People who carry a “G” instead of an “A” at a specific spot in their genetic code have roughly a six-fold higher risk of developing certain types of brain tumors, a Mayo Clinic and University of California, San Francisco study has found. The findings, published online in the journal Nature Genetics, could help researchers identify people at risk of developing certain subtypes of gliomas which account for about 20 percent of new brain cancers diagnosed annually in the U.S. and may lead to better surveillance, diagnosis and treatment.

Researchers still have to confirm whether the spot is the source of tumors, but if it’s not, “it is pretty close,” says senior author Robert Jenkins, M.D., Ph.D., a pathologist at the Mayo Clinic Cancer Center. “Based on our findings, we are already starting to think about clinical tests that can tell patients with abnormal brain scans what kind of tumor they have, just by testing their blood.”