Science in brief

RESEARCHERS IDENTIFY PROMISING CANCER DRUG TARGET IN PROSTATE TUMORS

Scientists at Dana-Farber Cancer Institute report they have blocked the development of prostate tumors in cancer-prone mice by knocking out a molecular unit they describe as a “powerhouse” that drives runaway cell growth.

In an article that appeared June 25 in an advanced online publication by the journal Nature, the researchers say the growth-stimulating molecule called p110beta — part of a cellular signaling network disrupted in several common cancers — is a promising target for novel cancer therapies designed to shut it down. The report’s lead authors are Shidong Jia, Zhenning Liu, Sen Zhang, and Pixu Liu.

The p110beta molecule and a counterpart, p110alpha, are “isoforms” — slightly different forms — of an enzyme called PI(3)K that is an intense focus of cancer research and drug development. PI(3)K is the linchpin of a cell-signal pathway that responds to growth factor signals from outside the cell.

When activated by growth factor receptors, PI(3)K turns on a cascade of genes and proteins that drives cells to divide and grow. The molecular accelerator is normally kept under control by a tumor-suppressor protein, PTEN, which acts like a brake to curb excess cell growth that could lead to cancer.

Mutations that inactivate PTEN — in effect releasing the brake on growth signals — are found in a significant proportion of prostate, breast, and brain tumors. The senior authors of the new report, Jean Zhao and Thomas Roberts, previously showed that blocking p110alpha protein inhibits cancerous growth induced by various cancer-causing proteins, such as Her2 and EGFR. With that knowledge in hand, the researchers, in collaboration with pharmaceutical companies, are developing p110alpha blockers.

SCIENTISTS FIND HOW NEURAL ACTIVITY SPURS BLOOD FLOW IN THE BRAIN: NEWFOUND MECHANISMS COULD BOLSTER UNDERSTANDING OF BRAIN IMAGING, AGING’S EFFECTS

New research from Harvard University neuroscientists has pinpointed exactly how neural activity boosts blood flow to the brain. The finding has important implications for our understanding of common brain imaging techniques such as fMRI, which uses blood flow in the brain as a proxy for neural activity.

The research is described in the June 26 issue of the journal Neuron. “When you see a brain image from fMRI studies, you are actually looking at changes in blood flow and oxygenation,” says Venkatesh N. Murthy, professor of molecular and cellular biology in Harvard’s Faculty of Arts and Sciences. “But because of the tight coupling between neural activity and blood flow, we are able to use the blood flow changes as a surrogate for brain activity. A better understanding of exactly how brain activity boosts blood flow should help us better read this process in reverse, which is what we do when interpreting fMRI images.”

While it represents only about 5 percent of the human body’s mass, the brain consumes 20 percent of the oxygen carried in its blood. Unlike muscle and other types of tissue, the brain has no internal energy stores, so all its metabolic needs must be met through the continuous flow of blood.

Murthy and colleagues studied mice and found that neurovascular coupling occurs through intermediary cells called astrocytes. By manipulating calcium levels, astrocytes can dilate or constrict blood vessels, depending on whether or not the cells are bound by neurotransmitters.

WORLD HEALTH ORGANIZATION CREATES NEW SURGICAL TOOL TO MAKE OPERATIONS SAFER EVERYWHERE

With major surgery now occurring at a rate of 234 million procedures per year — one for every 25 people — and studies indicating that a significant percentage of those procedures result in preventable complications and deaths, the World Health Organization (WHO) launched a new safety checklist for surgical teams to use in operating theaters, as part of a major drive to make surgery safer around the world.

“Preventable surgical injuries and deaths are now a growing concern,” said Margaret Chan, director-general of WHO. “Using the checklist is the best way to reduce surgical errors and improve patient safety.

Several studies have shown that in industrial countries major complications are reported to occur in 3-16 percent of inpatient surgical procedures, with permanent disability or death rates of approximately 0.4-0.8 percent. In developing countries studies suggest death rates of 5-10 percent during major surgery. Mortality from general anesthesia alone is reported to be as high as one in 150 in parts of sub-Saharan Africa. Infections and other postoperative complications are also a serious concern around the world. The studies suggest that approximately half of these complications may be preventable.

“Surgical care has been an essential component of health systems worldwide for more than a century,” said Atul Gawande, a surgeon and professor at Harvard University. “Although there have been major improvements over the last few decades, the quality and safety of surgical care has been dismayingly variable in every part of the world. The Safe Surgery Saves Lives initiative aims to change this by raising the standards that patients anywhere can expect.”

The Safe Surgery Saves Lives initiative is a collaborative effort led by the Harvard School of Public Health and involving more than 200 national and international medical societies and ministries of health in a effort to meet the goal of reducing avoidable deaths and complications in surgical care. The WHO Surgical Safety Checklist, developed under the leadership of Gawande, identifies a set of surgical safety standards that can be applied in all countries and health settings.

INVASIVE TREATMENT APPEARS BENEFICIAL FOR MEN AND HIGH-RISK WOMEN WITH CERTAIN TYPE OF ACUTE CORONARY SYNDROMES

An analysis of previous studies indicates that among men and high-risk women with a certain type of heart attack or angina an invasive treatment strategy (such as cardiac catheterization) is associated with reduced risk of rehospitalization, heart attack or death, whereas low-risk women may have an increased risk of heart attack, or death with this treatment, according to an article in the July 2 issue of JAMA.

Although an invasive strategy is frequently used in patients with unstable angina and non-ST-segment elevation myocardial infarction (NSTEMI; a type of heart attack with certain findings on an electrocardiogram), data from some trials suggest that this strategy may not benefit women, and may carry a possible higher risk of death or heart attack, according to background information in the article. “Thus, the benefit of an invasive strategy in women remains unclear. However, individual trials have not been large enough to explore outcomes reliably within subgroups,” the authors write.

For this study, an invasive strategy was defined as the referral of all patients with heart attacks and unstable angina for cardiac catheterization (a procedure that allows physicians to find and open potential blockages in the coronary arteries to help prevent heart attacks and death) prior to hospital discharge. A conservative treatment strategy was defined as a primary strategy of medical management and subsequent catheterization only for those patients with ongoing chest pain or a positive stress test.

INTERNATIONAL TEAM IDENTIFIES 21 NEW GENETIC RISK FACTORS FOR CROHN’S DISEASE: STUDY COMBINES EFFORTS OF THREE RESEARCH GROUPS, BRINGS TOTAL RISK SITES TO 32

An international consortium of Crohn’s disease researchers has combined data from three independent studies to identify 21 new genetic variants associated with the inflammatory bowel disorder, bringing the total number of risk factors to 32. Several of these are involved with the immune system’s initial response to pathogens, supporting earlier evidence that disruptions in a process called autophagy may lead to the disorder’s characteristic immune system overactivity. The report appears in the journal Nature Genetics and received early online release.

“This [study] greatly increases our knowledge of the genetic architecture of Crohn’s and gives us more detailed insight into the biological underpinnings of the disease,” says Mark Daly of the Massachusetts General Hospital (MGH) Center for Human Genetic Research and the Broad Institute of MIT and Harvard, the report’s senior author. “Better understanding of the precise functions of these genes and the molecular effects of Crohn’s-associated variants should lead us to novel strategies for therapies and, someday, prevention.”

RELAXATION RESPONSE CAN INFLUENCE EXPRESSION OF STRESS-RELATED GENES: GENOMIC STUDY FINDS COMMON BIOLOGICAL BASIS FOR EFFECTS OF MIND/BODY PRACTICES

How could a single, nonpharmacological intervention help patients deal with disorders ranging from high blood pressure to pain syndromes to infertility to rheumatoid arthritis? That question may have been answered by a study finding that shows that eliciting the relaxation response — a physiologic state of deep rest — influences the activation patterns of genes associated with the body’s response to stress. The collaborative investigation by members of the Benson-Henry Institute for Mind/Body Medicine at Massachusetts General Hospital (MGH) and the Genomics Center at Beth Israel Deaconess Medical Center (BIDMC) appears in the open-access journal PLoS One.

“For hundreds of years Western medicine has looked at mind and body as totally separate entities, to the point where saying something ‘is all in your head’ implied that it was imaginary,” says Herbert Benson, director emeritus of the Benson-Henry Institute and co-senior author of the PloS One report. “Now we’ve found how changing the activity of the mind can alter the way basic genetic instructions are implemented.”

Towia Libermann, director of the BIDMC Genomics Center and the report’s co-senior author, adds, “This is the first comprehensive study of how the mind can affect gene expression, linking what has been looked on as a ‘soft’ science with the ‘hard’ science of genomics. It is also important because of its focus on gene expression in healthy individuals, rather than in disease states.”