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Archive - Apr 2, 2015

Certain Archaea Freeze in Place and Go Dormant When Confronted by Viruses

The microbes could surrender to the harmless virus, but instead they freeze in place, dormant, waiting for their potential predator to go away, according to a study published online on March 31, 2015 in mBio. The article is entitled "Virus-Induced Dormancy in Archaeon Sulfolobus islandicus." University of Illinois researchers found that Sulfolobus islandicus organisms can go dormant, ceasing to grow and reproduce, in order to protect themselves from infection by Sulfolobus spindle-shaped virus 9 (SSV9). The dormant microbes are able to recover if the virus goes away within 24 to 48 hours--otherwise they die. "The microbe is hedging its bet," said Associate Professor of Microbiology Rachel Whitaker, who led the research at the Carl R. Woese Institute for Genomic Biology. "If they go dormant, they might die, but we think this must be better than getting infected and passing it on." Sulfolobus islandicus is a species of archaea (a domain of single-celled organisms distinct from bacteria) found in acidic hot springs (photo) all over the world, where free viruses are not as common as in other environments. These microbes will go dormant in the presence of just a few viruses, whether active or inactive. While inactivated virus particles cannot infect a host, Dr. Whitaker's lab found they could still cause dormancy, and ultimately, death in Sulfolobus islandicus. "People thought these inactivated viruses were just an accident, that they were just mispackaged," Dr. Whitaker said. "Now we know they are being sensed by the host so they are having an effect.

Single-Cell Analysis Used to Illuminate Acute Myeloid Leukemia (AML); Staggering Genetic Diversity Revealed; May Dictate Change of Approach for Battling This Type of Cancer

All living things--from dandelions to reindeer--evolve over time. Cancer cells are no exception, and are subject to the two overarching mechanisms described by Charles Darwin: chance mutation and natural selection. In new research, Carlo Maley, Ph.D., and his colleagues describe compulsive evolution and dramatic genetic diversity in cells belonging to one of the most treatment-resistant and lethal forms of blood cancer: acute myeloid leukemia (AML). The authors suggest the research may point to new paradigms in both the diagnosis and treatment of aggressive cancers, like AML. Dr. Maley is a researcher at Arizona State University's (ASU’s) Biodesign Institute and an Assistant Professor in ASU's School of Life Sciences. His work focuses on applying principles of evolutionary biology and ecology to the study of cancer. The group's latest findings [the group included collaborators from Fred Hutchinson Cancer Research Center, the University of Pennsylvania, and UCSF] were published online on April 1, 2015 in Science Translational Medicine. The article is titled “Single-Cell Genotyping Demonstrates Complex Clonal Diversity in Acute Myeloid Leukemia.” A tumor is a laboratory for evolutionary processes in which nature experiments with an immense repertoire of variants. Mutations that improve a cell's odds of survival are "selected for," while non-adaptive cells are weeded out in the evolutionary lottery. Genetic diversity therefore provides cancer cells with a library of possibilities, with some mutations conferring heightened resistance to attack by the body's immune system and others helping malignant cells foil treatments like chemotherapy. Generally speaking, the seriousness of a given cancer diagnosis may be linked with genetic diversity in cancerous cells.

CHOP Using Ultra-Small, Specially Formulated Nanoparticles to Target Neuroblastomas with High-Payload Drug Delivery; Animal Model Success Suggests Clinical Trials May Start within Next Year

Delving into the world of the extremely small, researchers are exploring how biodegradable nanoparticles can precisely deliver anticancer drugs to attack neuroblastoma, an often-deadly children's cancer. By bringing together experts in pediatric oncology with experts in nanotechnology, researchers at The Children's Hospital of Philadelphia (CHOP) aim to thread the needle of delivering effective doses of cancer-killing agents while avoiding toxicity in healthy tissues. The team's new research shows that this approach inhibits tumor growth and markedly prolongs survival in animal models. "These nanoparticles allow us to get more 'bang for the buck'--greater efficacy at lower total doses," said Garrett M. Brodeur, M.D., a pediatric oncologist and expert in neuroblastoma at CHOP. "The nanoparticles are designed to slowly deliver a drug to the tumor, where it kills multiplying cancer cells, with lower toxicity to the systemic circulation." Dr. Brodeur's group collaborated with a group of CHOP nanotechnology researchers led by Michael Chorny, Ph.D., in a study to be published in print May 1, 2015 in Cancer Letters. The Cancer Letters article was published online on February 12, 2015, and is titled “Nanoparticle Delivery of an SN38 Conjugate Is More Effective Than Irinotecan in a Mouse Model of Neuroblastoma." Dr. Chorny, in turn, led a study to be published in the May print issue of Biomaterials, in collaboration with Brodeur's group and with Robert Levy, M.D., and Ivan Alferiev, Ph.D., both members with Dr. Chorny of a cardiology research group at CHOP. That paper, which described how the team engineered the specially formulated nanoparticles, was published online on February 16, 2015, and is titled “"Nanoparticle-Mediated Delivery of a Rapidly Activatable Prodrug of SN-38 for Neuroblastoma Therapy." This approach, explained Dr.