New drug mutes more melanomas
Therapies targeted to a specific mutation in the BRAF gene can significantly reduce tumor burden in metastatic melanoma. But these therapies are not suitable for melanomas lacking the mutation, and even tumors carrying the BRAF mutation eventually become resistant to those therapies.
Using human melanoma tumors implanted into mice, Ann Richmond, Ph.D., and colleagues assessed the effectiveness of an experimental drug (RAF265) that inhibits a broader set of cellular enzymes than the BRAF-targeted drugs. They found that 71 percent of tumors responding to the drug had the “normal” (wild-type) BRAF; only 29 percent of responding tumors carried the BRAF mutation. Additionally, responsive tumors showed increased expression of genes involved with a number of cellular pathways involving cell growth and cancer development.
The findings, reported in the April 15 Clinical Cancer Research, suggest that RAF265 may be beneficial for patients not eligible for BRAF-targeted therapies and that gene expression profiling may be useful for selecting patients for RAF265 therapy.
The research was supported by grants from the National Cancer Institute (CA68485) of the National Institutes of Health and the T.J. Martell Foundation.
— Melissa Marino
Dengue antibodies give vaccine leadsResearchers working to produce a vaccine or treatment for dengue fever face a difficult road, because prior infection can sometimes make subsequent infections more severe, instead of milder. James Crowe, M.D., is a co-author on a study that draws a clearer picture of the powerful human antibodies produced by dengue fever survivors.
The investigators discovered that human antibodies reacted in a much weaker way than expected against proteins isolated from the virus (often used as a “subunit vaccine”) compared with the reaction to a whole virus particle. The human antibodies seemed to need the whole virus to work well. Using mapping techniques, the researchers found that a key binding site the best human antibodies use to neutralize dengue virus is a complex, bridged combination of two proteins on the virus’s envelope.
This information, published recently in the Proceedings of the National Academy of Sciences, may help speed development of an effective vaccine or treatment for dengue fever.
The research was supported by a grant from the National Institute of Allergy and Infectious Diseases (AI057157) of the National Institutes of Health.
— Carole Bartoo
Early stomach troubles augur anxiety
Children with stomach troubles grow up to be anxious adolescents and young adults, according to a recent study by Lynn S. Walker, Ph.D., and colleagues.
The researchers identified patients who underwent an upper GI scope because of gastroesophageal reflux (GERD) or functional dyspepsia (indigestion) between five and 15 years ago. About 100 of the former pediatric patients along with 143 healthy controls were asked to self-report on current stomach troubles, anxiety, quality of life and depression.
Adolescents and adults who had stomach problems in childhood had about double the rate of anxiety as those who did not, indicating an association between pediatric dyspepsia and anxiety the researchers characterize as “strong.” Increased risk of anxiety applied equally to those with normal esophageal histology and those with histologic esophagitis in childhood.
The results, published in the April issue of Gastroenterology, suggest that evaluation of psychological functioning should be considered as an integral part of the medical evaluation for dyspeptic symptoms.
The research was supported by grants from the National Institute of Child Health and Human Development (HD23264, HD15052), the National Institute of Diabetes and Digestive and Kidney Diseases (DK007673, DK058404) and the National Center for Research Resources (RR024975) of the National Institutes of Health.
— Carole Bartoo
Better blood pressure-reducing drugs?
Beta-blockers – commonly used to treat hypertension – lower blood pressure and reduce cardiovascular mortality in patients with coronary artery disease and congestive heart failure. But older beta-blockers like metoprolol can worsen glucose balance and inhibit fibrinolysis (the process that breaks down blood clots), which may be problematic for patients with obesity and metabolic syndrome.
Nancy Brown, M.D., and colleagues compared the effects of nebivolol, a third-generation beta-blocker, and metoprolol on glucose balance and markers of fibrinolysis in 46 subjects with metabolic syndrome. They found that the two medicines equivalently reduced blood pressure and heart rate. Metoprolol decreased insulin sensitivity and increased oxidative stress and markers of impaired fibrinolysis, whereas nebivolol lacked these detrimental metabolic effects.
The findings, reported in the April issue of Hypertension, suggest that nebivolol may be preferable for treating hypertension in obese patients with metabolic syndrome. Large-scale clinical trials are needed to fully compare the effects of nebivolol and metoprolol on clinical outcomes in such patients.
This research was supported by a grant from Forest Laboratories, Inc. and by funding through National Institutes of Health grants from the National Heart, Lung and Blood Institute (HL060906) and the National Center for Research Resources (RR024975).
— Leigh MacMillan
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