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Archive - Sep 23, 2013

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Hopkins Scientists Eliminate Human Brain Tumor Cells in Mice

Working with mice, Johns Hopkins researchers have discovered that weeks of treatment with a repurposed FDA-approved drug halted the growth of — and ultimately left no detectable trace of — brain tumor cells taken from adult human patients. The scientists targeted a mutation in the IDH1 gene first identified in human brain tumors called gliomas by a team of Johns Hopkins cancer researchers in 2008. This mutation was found in 70 to 80 percent of lower-grade and progressive forms of the brain cancer. The change occurs within a single spot along a string of thousands of genetic coding letters, and is disruptive enough to keep the seemingly innocuous protein from playing its role in converting glucose into energy. Instead, the mutation hijacks the protein to make a new molecule not normally found in the cell, which is apparently a linchpin in the process of forming and maintaining cancer cells. Encouraged by the new findings, described online on September 16, 2013 in the open-access journal Oncotarget, the Johns Hopkins researchers say they want to work quickly to design a clinical trial to bring what they learned in mice to humans with gliomas. Despite the growing understanding of IDH1 mutant gliomas, the development of effective therapies has proven challenging, they say. "Usually in the lab, we're happy to see a drug slow down tumor growth," says Alexandra Borodovsky, a graduate student in the Cellular and Molecular Medicine Program at the Johns Hopkins University School of Medicine, who performed the experiments. "We never expect tumors to regress, but that is exactly what happened here." "This therapy has worked amazingly well in these mice," says study leader Gregory J. Riggins, M.D., Ph.D., a professor of neurosurgery and oncology at the Johns Hopkins University School of Medicine.

Genotyping-by-Sequencing Used to Analyze Sorghum Genome; Results May Usher in New Uses for This Grain in Food and Fuel

Although sorghum lines underwent adaptation to be grown in temperate climates decades ago, a University of Illinois researcher said he and his team have completed the first comprehensive genomic analysis of the molecular changes behind that adaptation. Dr. Patrick Brown, an assistant professor in plant breeding and genetics, said having a complete characterization of the locations (loci) affecting specific traits will speed up the adaptation of sorghum and other related grasses to new production systems for both food and fuel. Dr. Brown is working on the project through the Energy Biosciences Institute (EBI) at the University of Illinois, hoping to use the sorghum findings as a launching pad for working with complex genomes of other feedstocks. The EBI provided the startup funding for the study. To adapt the drought-resistant, tropical sorghum to temperate climates, Dr. Brown explained that sorghum lines were converted over the years by selecting and crossing exotic lines with temperate-adapted lines to create lines that were photoperiod-insensitive for early maturity, as well as shorter plants that could be machine-harvested. "Surprisingly no one had ever really genotyped these lines to figure out what had happened when they were adapted," Dr. Brown said. "Now that genotyping is cheap, you can get a lot of data for a modest investment." Previous studies had looked at a specific genomic region or a smaller subset of these lines. "This is the first study to look at all of them. A previous paper had come out looking at a specific region of chromosome 6. What we did was not much more expensive, and we got a bigger picture that was completely technology enabled," he said. The results were published online on June 26, 2013 in an open-access article in Genome Biology.

Breakthrough Imaging Tool Developed for Multiple Sclerosis Diagnosis and Monitoring

Researchers have made an exciting breakthrough – developing a first-of-its-kind imaging tool to examine myelin damage in multiple sclerosis (MS). MS is an extremely difficult disease to diagnose, and the new tool is expected to help physicians diagnose patients earlier, monitor the disease’s progression, and evaluate therapy efficacy. Case Western Reserve University School of Medicine scientists have developed a novel molecular probe detectable by positron emission tomography (PET) imaging. The new molecular marker, MeDAS, offers the first non-invasive visualization of myelin integrity of the entire spinal cord at the same time, as reported online on September 23, 2013 in the Annals of Neurology. “While MS originates in the immune system, the damage occurs to the myelin structure of the central nervous system. Our discovery brings new hope to clinicians who may be able to make an accurate diagnosis and prognosis in as little as a few hours compared to months or even years,” said Yanming Wang, Ph.D., senior author of the study and associate professor of radiology at Case Western Reserve University School of Medicine. “Because of its shape and size, it is particularly difficult to directly detect myelin damage in the spinal cord; this is the first time we have been able to image its function at the molecular level.” As the most common acquired autoimmune disease currently affecting more than two million people worldwide, MS is characterized by destruction of myelin, the membrane that protects nerves (see image). Once damaged, the defective myelin inhibits the nerves’ ability to transmit electrical impulses, causing cognitive impairment and mobility dysfunction. So far, there is no cure for MS; therapies are only available that modify the symptoms.