PeopleÂ touched by a brain tumor — patients,Â their families or friends — may have heard of the drug Gliolan or 5-ALA, which is taken up preferentially byÂ tumor cells and makes them fluorescent. The idea behind it is straightforward: if the neurosurgeon can seeÂ the tumor’s boundaries better during surgery, he or she can excise it more thoroughly and accurately.
5-ALA is approved for use in Europe but is still undergoing evaluation by the U.S. FDA. A team at Emory was the first to test this drug in the United States.Â [Note:Â A similar approach, based on protease activation of a fluorescent probe, was reportedÂ last week in Science Translational Medicine.]
A hand-held device to detect glowing brain tumors could allow closer accessÂ to the critical areaÂ than a surgical microscope
Biomedical engineer Shuming Nie and colleagues recently described their development of a hand-held spectroscopic deviceÂ for viewing fluorescent brain tumors. This presents aÂ contrast withÂ the current tool, a surgical microscope — see figure.
Nie’s team testedÂ their technologyÂ on specimens obtained from cancer surgeries.Â Their paper in Analytical Chemistry reports:
The results indicate that intraoperative spectroscopy is at least 3 orders of magnitude more sensitive than the current surgical microscopes, allowing ultrasensitive detection of as few as 1000 tumor cells. Read more
Earlier today, weÂ posted a notice on Eurekalert for a Sunday, December 13 presentation by graduate student Jessica Konen at theÂ American Society for Cell Biology meeting in San Diego.
Her research, performed with Adam Marcus at Winship Cancer Institute, was the topic of a video that recently won first prize in a contest sponsored by the Association of American Medical Colleges. ThisÂ was our video team’s first use of theÂ “fast hand on whiteboard” effect, and a lot of fun to make. The video’s strength growsÂ out of the footageÂ Konen and Marcus have of cancer cells migrating in culture. Check it out, if you haven’t already.
PosterÂ presentations at the 2015 ASCB meeting can be found by searching this PDF. A few Emory-centric highlights:
*Chelsey Ruppersburg and Criss Hartzell’s work on the “nimbus”, a torus-shaped structure enriched in proteins needed to build the cell’s primary cilium
*Anita CorbettÂ on how Emory students have a strong record of attaining their own NIH research funding
*Additional work by Adam Marcus’ lab on the tumor suppressor gene LKB1 and how its loss drives lung cancer cells to take on a “unique amoeboid morphology”
*Research from David Katz’s lab on the “epigenetic eraser” LSD1 (lysine-specific demethylase) and its function in neurons and neurodegeneration Read more
Graft-vs-host disease is a common and potentially deadly complication following bone marrow transplants, in which immune cells from the donated bone marrow attack the recipientâ€™s body.
Winship Cancer Instituteâ€™s Ned Waller and researchers from Childrenâ€™s Healthcare of Atlanta and Yerkes National Primate Research Center were part of a recent Science Translational Medicine paper that draws a bright red circle around aurora kinase A as a likely drug target in graft-vs-host disease.
Aurora kinases are enzymes that control mitosis, the process of cell division, and were first discovered in the 1990s in yeast, flies and frogs. Now drugs that inhibit aurora kinase A are in clinical trials for several types of cancer, and clinicans are planning to examine whether the same type of drugs could help with graft-vs-host disease.
Leslie Kean, a pediatric cancer specialist at Seattle Childrenâ€™s who was at Emory until 2013, is the senior author of the STM paper. Seattle Childrens’ press releaseÂ says that Kean wears a bracelet around her badge from a pediatric patient cured of leukemia one year ago, but who is still in the hospital due to complications from graft-vs-host. Read more
What do cancer cells have in common with horseshoe crabs and Mr. Spock from Star Trek?
They all depend upon copper. Horseshoe crabs have blue blood because they use copper to transport oxygen in their blood instead of iron (hemocyanin vs hemoglobin). Vulcansâ€™ blood was supposed to be green, for the same reason.
Horseshoe crabs and Vulcans use copper to transport oxygen in their blood. Cancer cells seem to need the metal more than otherÂ cells.
To be sure, all our cells need copper. Many human enzymes use the metal to catalyze important reactions, but cancer cells seem to need it more than healthy cells. Manipulating the bodyâ€™s flow of copper is emerging as an anticancer drug strategy.
A team of scientists from University of Chicago, Emory and Shanghai have developed compounds that interfere with copper transport inside cells. These compounds inhibit the growth of several types of cancer cells, with minimal effects on the growth of non-cancerous cells, the researchers report in Nature Chemistry.
â€œWeâ€™re taking a tactic that’s different fromÂ other approaches. These compounds actually cause copper to accumulate inside cells,â€ says co-senior author Jing Chen, PhD, professor of hematology and medical oncology at Emory University School of Medicine and Winship Cancer Institute. Read more
The DNA in our cells is constantly being damaged by heat, radiation and other environmental stresses, andÂ the enzyme systems that repair DNA are critical for life. A particularly toxic form of damage is the covalent attachment of a protein to DNA, which can be triggered by radiation or by anticancer drugs.
Keith Wilkinson, PhD
Emory biochemist Keith Wilkinson and colleagues have a paper this week in the journal eLife probing how a yeast protein called Wss1 is involved in repairing DNA-protein crosslinks. The researchers show how Wss1 wrestles with a protein tag called SUMO onÂ the site of the DNA damage, and how Wss1 and SUMO areÂ involved in the cleanup process.
Three interesting things about this paper:
*The paper grew out of first author Maxim Balakirevâ€™s sabbatical with Wilkinson at Emory. Balakirev’s home base is at the CEA (Alternative Energy and Atomic Energy Commission)Â in Grenoble, France.
* Since manyÂ cancer chemotherapy drugs induce protein-DNA cross links, an inhibitor of cross linkÂ repair could enhance those drugs’ effectiveness. On the other side of the coin, mutations in a human gene called Spartan, whose sequence looks similar to Wss1â€™s, cause premature aging and susceptibility to liver cancer. Whether the Spartan-encoded protein has the same biochemical activity as Wss1 is not yet clear.
*SUMOÂ stands for â€œsmall ubiquitin-like modifierâ€. The eLife digest has an elegant explanation of whatâ€™s happening: Read more
Evolutionary theory says mutations are blind and occur randomly. But in theÂ controversialÂ phenomenon of adaptive mutation, cells can peek under the blindfold, increasing their mutation rate in response to stress.
Scientists at Winship Cancer Institute, Emory University have observed that an apparent “back channel” for genetic information called retromutagenesis can encourage adaptive mutation to take place in bacteria.
The results were published Tuesday, August 25 inÂ PLOS Genetics.
“This mechanism may explain how bacteria develop resistance to some types of antibiotics under selective pressure, as well as how mutations in cancer cells enable their growth or resistance to chemotherapy drugs,” says senior author Paul Doetsch, PhD.
Doetsch is professor of biochemistry, radiation oncology and hematology and medical oncology at Emory University School of Medicine and associate director of basic research at Winship Cancer Institute. The first author of the paper is Genetics and Molecular Biology graduate student Jordan Morreall, PhD, who defended his thesis in April.
Retromutagenesis resolves the puzzle: if cells arenâ€™t growing because theyâ€™re under stress, which means their DNA isnâ€™t being copied, how do the new mutants appear?
The answer: a mutation appears in the RNA first. Read more
As a followup to yesterday’s post on following troublemaker cells in patients with lupus, we’d like to highlight a recent paper in Blood that takesÂ a similar approach to studying how the immune system comes back after bone marrow/blood stem cell transplant.
Leslie Kean, MD, PhD
The paper’sÂ findings have implications for making this type ofÂ transplant safer and preventing graft-versus-host disease.Â In a bone marrow/blood stem cell transplant, to fight cancer, doctors are essentially clearing out someone’s immune system and then “planting” a newÂ oneÂ with the help of a donor. What this paper shows is how much CMV (cytomegalovirus) distorts the new immune system.
CMV is often thought of asÂ harmless — most adults in the United States have been infected with CMV by age 40 and don’t get sick because of it. But in this situation, CMV’s emergence from the shadows forces some of the new TÂ cells to multiply, dominating the immune system so much that it creates gaps in the rest of the T cell repertoire, which canÂ compromise protective immunity. Other seemingly innocuous viruses like BK cause trouble in immunosuppressed patients afterÂ kidney transplant.
The senior author, Leslie Kean, moved from Emory to Seattle Children’s Hospital in 2013, and her team began these studies here in 2010Â (a host of Emory/Winship hematologists and immunologists are co-authors).Â This paperÂ is sort of a mirror image of the Nature Immunology paper on lupus because it also uses next-generation sequencing to follow immune cells with DNA rearrangements — in this case, T cells. Read more