March 31, 2011

Aliquots — research highlights from VUMC laboratories


Blood vessel factors spur tumor growth

Tumors often produce factors that stimulate growth of new blood vessels. These vessels then bring in more oxygen and nutrients to fuel the tumor’s continued growth and spread. Researchers have suspected that these vessels might also secrete factors that influence tumor growth independent of their nutrient delivery functions.

Jin Chen, M.D., Ph.D., Dana Brantley-Sieders, Ph.D., and colleagues have now identified one of these secreted factors, Slit2, and describe its influence on tumor behavior in the Feb. 1 issue of Cancer Research. Using cultured cells, they show that increasing Slit2 expression impairs tumor growth and motility – suggesting it acts as a tumor suppressor. Additionally, EphA2 – a protein important in angiogenesis and often over-expressed in tumors – suppresses expression of Slit2.

In human breast cancers, high levels of EphA2 correlated with low Slit2 expression and higher Slit2 expression in these tumors predicted better prognosis. The findings suggest that targeting signals like Slit2 or factors that regulate it (like EphA2) may provide new options for treatments to prevent recurrence and metastasis.

— Melissa Marino


Gene ups risk for needing pacemaker

Sick sinus syndrome (SSS) – a disorder that slows the heart rate and increases the risk for atrial fibrillation – is the most common reason for implanting a cardiac pacemaker.

Dawood Darbar, M.D., Dan Roden, M.D., and colleagues at deCODE genetics in Iceland have identified a novel susceptibility gene (MYH6) that increases the risk for developing SSS. MYH6 encodes a myosin protein that is part of the heart’s contractile machinery. The investigators identified a rare variant in the gene that confers a 50 percent lifetime risk of SSS(individuals who do not carry the variant have a 6 percent risk). The researchers also showed that other common variants in MYH6 affect heart rate, demonstrating the interplay between common and rare genetic variants in complex diseases.

The findings in Nature Genetics establish the importance of cardiac myosin in the development of heart rhythm disorders. The Vanderbilt AF Registry, an ongoing clinical and DNA registry of patients with atrial fibrillation, contributed patient samples to the study.

— Leigh MacMillan


How young brains make sense of senses

When two sensory inputs – a sight and a sound – occur close in time, the adult brain can “bind” them and conclude that they result from a single event (synchronous). However, infants have a larger “temporal window” than adults and bind events that are more distant in time. Little is known about how this capacity develops during childhood.

Wellcome Images

Wellcome Images

Mark Wallace, Ph.D., and colleagues compared the ability of 10- and 11-year olds and adults to detect asynchrony of a visual (image on computer screen) and an auditory (tone) stimulus. Like infants, children had a much larger temporal window than adults. And children were more likely to call events “simultaneous” when the auditory stimulus came before the visual stimulus – but not vice versa.

The findings, reported in the February issue of Neuropsychologia, show that this process continues to develop into the second decade of life. Because abnormalities in multisensory processing may contribute to disorders such as autism and dyslexia, this information could inform diagnostic strategies and interventions for these disabilities.

— Melissa Marino


Pre-meal grapefruit battles bulge

Eating a low “energy dense” (calories per gram of food) food item before a meal appears to increase feelings of fullness and can reduce overall caloric intake. The optimal form of a low energy dense “preload” – solid, semi-solid or liquid – is still being debated.

Heidi Silver, Ph.D., R.D., and colleagues compared a solid (grapefruit), liquid (grapefruit juice), or water preload before each of three main meals daily in obese adults following a calorie-restricted diet for 12 weeks. Average overall weight loss was 7.1 percent, with no difference between the three groups. Each of the preloads reduced total average dietary energy density and total energy intakes. It appears that participants compensated for the preloads by choosing to eat foods with lower energy density. Grapefruit and grapefruit juice preload groups had increased (desirable) HDL-cholesterol levels.

The findings reported in Nutrition & Metabolism suggest that adding a low energy dense dietary preload to a calorie-restricted diet is an effective weight loss strategy. The form of the preload is open to individual choice, but some preloads have important cardiometabolic benefits.

— Leigh MacMillan


We welcome suggestions for research to highlight in Aliquots. The items should be primary research articles (no reviews, editorials or commentaries) published within the last two months in a peer-reviewed journal. Please send the article citation (PDF if available) and any other feedback about the column to:

Past Aliquots

June 22, 2012
June 8, 2012
May 11, 2012
April 27, 2012
April 13, 2012
March 30, 2012
March 16, 2012