Researchers have shown that a marker in tissue surrounding tumor cells is a new prognostic factor for patients with breast cancer. Absence of the market (caveolin-1) in stromal fibroblasts is associated with early disease recurrence, metastasis, and decreased patient survival. Stroma is non-cancerous connective tissue, which, in solid tumors, surrounds tumor cells. “The idea that a prognostic biomarker is present in the stroma rather than the epithelial cancer cell is paradigm-shifting,” said Dr. Michael Lisanti, the senior of the study and editor-in-chief of the American Journal of Pathology. “Importantly, these findings could be developed into a diagnostic test that would not require DNA-based technologies. This inexpensive and cost-effective test would allow doctors to identify high-risk breast cancer patients at diagnosis and treat them more aggressively.” The absence of caveolin-1 in the stroma also appeared to be a marker for drug resistance in patients receiving the anti-cancer drug tamoxifen, the researchers said. “These are significant findings that do have to be validated in prospective breast cancer clinical trials,”said Dr. Richard Pestell, director of the Kimmel Cancer Center at Thomas Jefferson University, and an author of the study. “However, we should start taking the breast tumor stroma into our clinical considerations sooner, rather than later.” The study appears in the May 1 online edition of American Journal of Pathology, together with another group’s study on stromal expression of caveolin-1 in breast cancer. A related study was published online in Cancer Biology & Therapy.
Gold Nanorods May Permit Heat Treatment of Tumors
Scientists at MIT, together with collaborators, have developed gold nanorods that can home in on tumors and then, by absorbing energy from near-infrared light and emitting it as heat, destroy the tumors with minimal side effects. The light heats the nanorods, but passes harmlessly through tissue. Although it has long been known that heat can kill tumor cells, it has previously been difficult to heat the tumor cells specifically while leaving the surrounding tissue undamaged. In designing the nanorods, the researchers took advantage of the fact that blood vessels located near tumors have tiny pores just large enough for the nanorods to enter. The team developed a polymer coating for the particles that allows them to survive in the bloodstream longer than any other gold nanoparticles. In experiments in mice with tumors, the nanorods were injected into the bloodstream and accumulated in the tumors. With near-infrared laser treatment, the tumors disappeared in 15 days. The treated mice survived for three months with no evidence of recurrence, until the end of the study, while mice that received no treatment or only the nanorods or laser, did not. The researches noted that the gold nanorods also have potential in the detection and diagnosis of tumors, because the particles can be imaged by a technique known as Raman scattering. This work was reported in two recent papers, one in Cancer Research and the other in Advanced Materials. [MIT release]
Primordial Gene Might Permit Bypass of Mitochondrial Defects
Researchers have shown that by providing Parkinson-disease-model fruit flies with a gene they don’t normally possess, they can rescue the flies from their Parkinson-like symptoms, including movement defects and excess free radicals produced in mitochondria. The key gene (single-subunit alternative oxidase or AOX) essentially acts as a bypass for blockages in the so-called oxidative phosphorylation (OXPHOS) cytochrome chain in mitochondria. Dr. Howard Jacobs, who led the study at the University of Tampere in Finland, likens that chain to a series of waterfalls in a hydroelectric power station. Only, in the case of mitochondria, it is electrons that flow to release energy that is captured in molecular form. Defects in mitochondrial OXPHOS are associated with diverse and mostly intractable human disorders, the researchers said. Therefore, there’s a chance that the strategy might also prove beneficial in mammals, including humans, which, like insects, have also lost the AOX gene over the course of evolution. On the other hand, most plants, animals, and fungi do possess an alternative mitochondrial respiratory chain, which can bypass the OXPHOS system under specific physiological conditions. Their findings led the researchers to conclude that “AOX appears to offer promise as a wide-spectrum therapeutic tool in OXPHOS disorders.” “OXPHOS dysfunction is not just a problem in some rare genetic disorders or in degenerative diseases,” Dr. Jacobs added. It’s an issue in a very large number of pathologies—and a major cause of tissue damage after heart attack and stroke.
Next-Gen Sequencing Speeds Mutation Mapping in Fruit Flies
A novel whole-genome sequencing approach using Illumina next-generation sequencing technology has been developed and used for mapping single-base mutations in the fruit fly. The novel methodology promises to reduce the time and effort required to identify mutations of biological interest. “This approach will change the way fruit fly genetics is done,” said Scott Hawley, Ph.D., a co-equal senior author on the publication. “Traditional mapping approaches to identify mutations are inefficient procedures. Our whole-genome sequencing approach is fast and cost-effective. Among other potential uses, it also carries the potential to pinpoint inheritable molecular characteristics that are controlled by several genes at once.” Model organisms like fruit flies are used in research for studying both normal biological processes and human disease. Fruit fly genes can be inserted, deleted, or modified, and large numbers of flies can be randomly mutated to generate interesting phenotypes relevant to human disease. Finding the mutated gene responsible for an interesting phenotype is currently labor-intensive and time-consuming, and many mutations that cause medically relevant phenotypes are not discovered. The new approach lowers the barrier to finding mutations and may greatly accelerate the discovery of genes important for human health, the researchers suggest. The study was published in the May issue of Genetics. [Stowers Institute release] [Genetics abstract]
Study Supports Role of Autoimmunity in Narcolepsy
An immune system gene has been strongly associated with a form of narcolepsy, lending strength to the long-held belief that this sleep disorder is an autoimmune disease. The researchers suggest that this finding could have implications not just for narcolepsy, but for a wide range of autoimmune diseases. The gene is TCRA (T-cell receptor alpha), which codes for a receptor protein on T-cells. Narcolepsy is a disorder that causes disabling daytime sleepiness, irresistible bouts of sleep that can strike at any time, and disturbed sleep at night. This new study focused on a special form of the disease called narcolepsy with cataplexy, which is a sudden loss of muscle tone that can cause a person to collapse, with or without falling asleep. Approximately 1 in 2,000 people in the United States have narcolepsy-cataplexy. The symptoms of this disease have been shown to result from the death of a small group of brain cells that normally regulate the sleep-wake cycle by releasing hormone chemicals called hypocretins. Previous work had shown that almost everyone with narcolepsy-cataplexy has the same variant (HLA-DQB*0602) of a major histocompatibility gene. Because of HLA’s prominent role in immunity, it was hypothesized that narcolepsy-cataplexy might be caused by an autoimmune attack on the hypocretin-producing cells in the brain. The new study lends credence to this theory by implicating an immune system gene (TCRA).
Birdsong of Isolated Finches Reverts to Normal Over Several Generations
Researchers have shown that the abnormal song of isolated male zebra finches reverts to normal over several generations of one-on-one “tutor-pupil” pairings with a new generation of male finches (the pupils). Male finches typically learn their song from other male finches. In the experiments, the pupil finches imitated their tutors’ songs, but changed certain characteristics. The alterations accumulated over generations. By the fourth generation, the original isolate’s song had evolved toward the wild-type song. “Culture appears to be encoded in the birds. It just needed a few generations to emerge,” said the senior author of the study. He noted that the same pattern of evolution in the song occurred whether the subsequent generations of male birds were raised among female birds (who do not sing) and siblings in a colony setting, or just among isolate males one-on-one. The results were published in the May 3 online edition of Nature. [Press release] [Wired News story] [Science Daily story] [Nature abstract]
Qatar Researchers Establish Draft Genome Sequence for Date Palm Tree
Using next-generation sequencing technology, researchers at the Weill-Cornell Medical College in Qatar (WCMC-Q) have determined a draft genome sequence for the date palm tree. Date palm trees play a significant role in agriculture throughout the Middle East, Northern Africa, and Pakistan. The fruit is a major source of nutrition in those areas, and the tree itself plays an important role in the development of sustainable agriculture in many drought- and saline-affected regions of the world. References in the Qur’an have kept alive the use of dates for medicinal purposes over the centuries. Genetic information about the date palm is expected to be extremely valuable to researchers who are working to improve fruit yield and quality and to better understand susceptibility and resistance to disease. The date palm sequencing work was a proof-of-concept study, according to Joel Malik, director of the Genomics Laboratory at the WCMC-Q, who established the genomics laboratory last year. The goal was to establish and validate the capabilities of the core lab for large-scale genomics projects. The lab is an integral part of a large biomedical research program launched last year by the WCMC-Q, with support from the Qatar Foundation, that aims to make Qatar a hub for research in the Middle East. [Press release]
Non-Native Beetle Destroying Oaks in Southern California
A beetle first detected in California in 2004 has now attacked 67 percent of the oak trees in an area 30 miles east of San Diego, according to a recent report. The beetle is Agrilus coxalis and the reporting researchers have proposed that it be given the common name: goldspotted oak borer. Land managers and scientists are concerned about further spread of the beetle infestation because oaks are the dominant tree species in the area. Further tree mortality will increase fire danger and decrease wildlife habitat in southern California. The managers and scientists are also concerned that drought and climate change will make more oaks susceptible to this insect that is not native to California. Oak trees have a nearly continuous distribution in the state, reaching from the infestation area north to the Oregon border. “We don’t know how the beetle arrived in San Diego County because there’s a broad barrier of desert around the localities where it was previously collected in Arizona, Guatemala, and Mexico,” said one of the study’s authors. “We suspect it was either recently brought to California or somehow expanded its range.” There are reports of oak firewood from Mexico frequently being brought into the area in the past 20 years and that could be how it was introduced, the scientist said. Further research is necessary to determine how to halt the spread of the beetle infestation. [Press release]
Nitric Oxide Nanoparticles Show Promise in Treating Staph Infections
Researchers at the Albert Einstein College of Medicine have shown that nanoparticles containing nitric oxide (NO) gas are effective in the topical treatment of drug-resistant Staphylococcus aureus infections in mice. “As the particles take on water, they loosen up and the nitric oxide slowly trickles out, releasing specific amounts of the gas—which is exactly what happens in your body,” said a senior author of the study. NO is produced normally by many cells throughout the body and has several important biological functions including killing bacteria, healing wounds, and increasing blood flow by dilating blood vessels. Until now, however, the delivery of NO to infection sites has proven difficult. S. aureus bacteria cause the majority of superficial and invasive skin infections, resulting in more than 11 million outpatient/emergency room visits and 464,000 hospital admissions annually in the U.S. S. aureus infections can be deadly if the bacteria invade the bloodstream, heart, lungs, or urinary tract. As more strains of S. aureus become resistant to common antibiotics, the need for new treatments has become urgent. The encouraging results in mice, followed by additional experiments, may pave the way for clinical trials in humans. [Press release]
Synthetic Mimic of Abscisic Acid May Protect Crops from Drought
Scientists have identified a synthetic chemical that has the potential to be used in a spray to protect crops that are facing drought conditions. The chemical is pyrabactin and it mimics abscisic acid (ABA), which is a plant stress hormone that helps crops survive stressful conditions such as drought. For years, scientists have contemplated spraying ABA directly onto crops to enhance their protection in times of stress. But ABA is a costly, complicated, and light-sensitive molecule that has not found use in agriculture. “We screened thousands of chemicals for one that mimics ABA,” said the senior author of the study. “We found pyrabactin activates some of the ABA receptors in plants and is an excellent mimic of ABA. Moreover, unlike ABA, it is stable and easy to make. It therefore suggests a highly effective chemical strategy for improving plants’ ability to survive under low-water conditions, potentially benefiting farmers in drought-prone areas worldwide.” The researchers also used the pyrabactin molecule to fish out an ABA receptor, believed to be the first such receptor to be definitively identified. This work was published online in the April 30 issue of Science Express. [Press release] [Science Express abstract]