In brief (June 2014) – Aspirin and influenza, evolution of self-control, celecoxib and cancer

Three picks among what I’ve read in the past months:
aspirin, prostaglandin E2, and influenza, or how blocking the production of prostaglandin E2 can help in the fight against influenza A virus
evolution of self-control, or how absolute, not relative, brain size correlates with cognition across species
drug repurposing, or how celecoxib, a non steroidal anti-inflammatory agent used in arthritis, may help to inhibit the formation of new blood vessels, tumor growth, and metastasis in mice.

  • Aspirin, prostaglandin E2, and influenza

Aspirin became popular during the Spanish Influenza A virus pandemic of 1918-1919 and has since commonly been used to relieve flu symptoms. Canadian researchers have now added one reason to why aspirin may be helpful in the fight against the flu virus, besides reducing fever and aches

The team found that mice genetically modified to be unable to produce prostaglandin E2, a lipid mediator known to modulate immune responses, fared better when infected with influenza A virus than control mice. Experiments revealed that prostaglandin E2 impaired the immune response against influenza A virus by blocking the production of type I interferon (an important antiviral molecule) in lung macrophages, thereby decreasing both innate and adaptive immunity. Prostaglandin E2 is produced by the sequential action of the enzymes cyclooxygenase and prostaglandin E synthase. Since aspirin works by blocking cyclooxygenase, it will block the production of prostaglandin E2 and therefore prevent it from impairing the immune response against the influenza virus. However, as blocking cyclooxygenase abolishes the production of many other molecules besides prostaglandin E2, all of which are involved in many different biological processes, it may be better to try and block more specifically the production of prostaglandin E2 by targeting the prostaglandin E synthase if what one wants is a treatment against influenza infection. The researchers found that pharmacological inhibition of prostaglandin E synthase reduced the mortality rate of mice lethally infected with influenza A virus, and that the treatment was still effective when given 2 or 3 days after infection. Targeting prostaglandin E synthase may therefore be a potential therapeutic approach to treat influenza A infection.

(Coulombe F et al, Immunity 17 April 2014. doi: 10.1016/j.immuni.2014.02.013)

  • Evolution of self-control

In a study published in PNAS in May, a large number of experimental psychologists and animal behaviorists joined efforts to study the performance of 36 species on tasks related to self-control and reflect on the current hypotheses regarding cognitive evolution in view of their results. This study is interesting for several reasons:

– the number and diversity of species included in this one study (from elephants to pigeons via primates and dogs) allowed the researchers to analyze cognitive performance across species based on comparable experimental procedures and within a phylogenetic framework (how the species relate to one another on the evolutionary tree)
– the results revealed that absolute brain size was the best predictor for a species’ performance on the self-control tasks: species with bigger brains were better at controlling their immediate response to a stimulus in favor of a previously learned routine (imagine learning to retrieve food from an opaque container, and when subsequently presented with food in a transparent container, refrain from reaching for the food directly and thus bumping into the container, but instead retrieve the food as you have previously learned)
relative brain size only weakly correlated with cognitive performance (the relative brain size takes into account the body size of a species; for example, humans have a bigger brain than what would be expected considering their body size, based on other mammals with comparable body mass)
– the fact that absolute, but not relative, brain size predicted cognitive performance (when it comes to self-control) supports the idea that cognition is associated with reorganization of the brain as it becomes bigger, rather than with just having “extra neurons” (having a bigger brain than what is expected given the body size)
within primates, diet breadth was correlated to levels of self-control, but group size was not, which is surprising considering the popular hypothesis that social group size was critical to the evolution of primate cognition.

For further discussion of these results, I highly recommend reading the following post by John Hawks: Forget EQ. Forget “Machiavellian intelligence”.
Another good read on this topic, the following post by Ed Yong: This is how you study the evolution of animal intelligence.

(MacLean E et al, PNAS 20 May 2014. doi: 10.1073/pnas.1323533111)

  • Drug repurposing

Angiogenesis, the formation of new blood vessels, is a characteristic feature of malignant tumors. Blood vessels not only convey the nutrients that fuel tumor growth but also constitute a route for tumor cells to spread to other body sites. The main molecule recognized to stimulate angiogenesis is called vascular endothelial growth factor (VEGF), and drugs blocking the VEGF pathway are used in the treatment of several types of cancer. However, these therapies have only achieved modest and transient effects, mostly because the tumor cells can activate alternative pathways to promote angiogenesis.

Searching for molecules that could support angiogenesis independently of the VEGF pathway, American researchers found that production of prostaglandin E2 (PGE2) by tumor cells correlated with their tumorigenic potential. Additional experiments suggested that the COX-2/PGE2 pathway could promote angiogenesis in a VEGF-independent way (COX-2, or cyclooxygenase 2, is a critical enzyme in the PGE2 production chain). Combination of celecoxib, a COX-2 inhibitor used in the treatment of arthritis, with another agent blocking the VEGF pathway appeared more effective than either single drug at blocking metastasis in two preclinical colon and breast cancer models in mice. Altogether, the authors of the study suggest that drugs blocking the COX-2/PGE2 pathway might be of benefit in combination with other antiangiogenic agents in certain types of cancer. Controlled clinical trials will be required to confirm (or infirm) such a possibility.

(Xu L et al, Science Translational Medicine 25 June 2014. doi: 10.1126/scitranslmed.3008455)

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