What causes brain cancer?

Glioblastoma is the most common and most lethal form of brain tumor in people. Research published in the International Journal of Computational Biology and Drug Design offers a novel way to determine what biological functions go awry when the tumor first begins to form. Understanding the problems at the molecular level might one day reveal the underlying mechanism of carcinogenesis in glioblastoma and ultimately lead to treatments or even preventative measures.

This form of brain tumor account for more than half of all cases in which the tumor is within the tissues of the brain and a fifth of cases in which a tumor is present within the skull.

Zhongming Zhao and colleagues at Vanderbilt University, in Tennessee, explain how problems that occur during the transcription of the genetic code for making proteins may play a role in the formation of a glioblastoma. These might arise through changes in the genetic materials itself or alterations to the molecules involved in regulating the transcription process. In their latest research, the team has tested the possibility that microRNAs (miRNAs) and transcription factors (TFs) might somehow regulate the genes glioblastoma. With this in mind, the researchers carried out a computer search of appropriate databases to uncover any links between these components of the genetic machinery and glioblastoma.

Although cancer exists in many different forms and is not a single disease but a complex array of different diseases, there are certain characteristics that define the different forms: self-sufficiency in growth signals, insensitivity to antigrowth signals, evading programmed cell death, limitless replicative potential of cells, sustained blood-vessel growth, evasion of the immune system, tissue invasion and spreading through the body in metastasis. Insights into these processes at the molecular level is now possible thanks to the advent of vast databases of genomic and biochemical information related to different types of cancer.

The Vanderbilt team has now searched three databases miR2Disease, HMDD (human miRNA-associated disease database) and PhenomiR, to find regulatory networks specific to glioblastoma. To do so they integrated data on glioblastoma-related miRNAs, TFs and genes. They utilized a well-known target-prediction tool, TargetScan, to trawl the databases and identified 54 so-called feed-forward loops (FFLs), these are molecular control systems involved in transcription and the required signaling processes. Follow up work revealed these FFLs to have functions important to carcinogenesis as well as unique functions specific to each FFL.

“Our work provided data for future investigation of the mechanisms underlying glioblastoma and also potential regulatory subunits that might be useful for biomarker discovery and therapy targets for glioblastoma,” the team concludes.

Gong, X., Sun, J., & Zhao, Z. (2011). Gene regulation in glioblastoma: a combinatorial analysis of microRNAs and transcription factors International Journal of Computational Biology and Drug Design, 4 (2) DOI: 10.1504/IJCBDD.2011.041006

Nanotech Viagra patch

Sildenafil citrate, commonly known as Viagra, is currently the first choice drug for erectile dysfunction but despite its success oral delivery of the drug is hampered by numerous side effects, the long delay before it starts working and the short amount of time it lasts. Researchers in Egypt think they may have a solution via nanotechnology.

Writing in the International Journal of Nanotechnology, the team describes tests on different formulations for sildenafil citrate transdermal nanocarriers as the delivery agent on human skin rather than the user having to swallow a pill. The benefits of such nanocarriers are that the drug gets into the bloodstream through the skin much more quickly than having to be ingested. Moreover, 70% of an oral dose of sildenafil citrate is wasted as it is metabolized by the liver without having any effect. Improved delivery via the transdermal route would avoid several side-effects as well as making onset of activity much quicker.

Pharmaceutical scientist Yosra S.R. Elnaggar of Alexandria University and professors there and at Alexandria and Pharos University, explain how previous attempts to create a Viagra transdermal application have been hampered by the properties of the drug itself. The drug has low oil and water solubility and is loathe to cross membranes, such as human skin, because of this. However, it is possible to encapsulate the drug in nanoemulsion based systems that can cross membranes readily. As such, the team has investigated two types of nanocarriers made using fat-like lipid molecules – the first made by forming an emulsion with the drug using a surfactant compound to allow the lipid molecules and drug to mix, much as soap will emulsify oil and water. The second option is a self-emulsifying nanocarrier that has its own inbuilt surfactant.

The team demonstrated in the laboratory that both formulations would have benefits for oral drug delivery, whereas only the nano-emulsion, rather than the self-emulsifying formulation, shows promise for a Viagra patch, in other words.

Elnaggar, Y., Massik, M., & Abdallah, O. (2011). Sildenafil citrate nanoemulsion vs. self-nanoemulsifying delivery systems: rational development and transdermal permeation International Journal of Nanotechnology, 8 (8/9) DOI: 10.1504/IJNT.2011.041443

Nitrogen-fixing aliens

Scientists hope that Titan, a moon of Saturn, with its nitrogen-rich atmosphere, could act as a model system for terrestrial chemistry before life began on our planet. Now, another step towards that goal has emerged as researchers at the University of Arizona have incorporated atmospheric nitrogen into organic macromolecules under conditions resembling those on Titan.

“Titan is so interesting because its nitrogen-dominated atmosphere and organic chemistry might give us a clue to the origin of life on our Earth,” explains Hiroshi Imanaka, who is an assistant research scientist in the UA’s Lunar and Planetary Laboratory. “Nitrogen is an essential element of life.” Titan looks orange through a telescope because its atmosphere is a rich smog of organic molecules. Particles in the smog could settle on the surface and be exposed to conditions that might eventually create life, said Imanaka.

Saturn's A and F rings, the small moon Epimetheus and the smog-enshrouded Titan, Saturn’s largest moon. (Credit: NASA/JPL/Space Science Institute)
Saturn's A and F rings, the small moon Epimetheus and the smog-enshrouded Titan, Saturn’s largest moon. (Credit: NASA/JPL/Space Science Institute)

Of course, nitrogen alone is not enough, nitrogen molecules must be converted to a chemically active form that can drive the necessary biochemical reactions that underpin biological systems.

Imanaka and Mark Smith converted a nitrogen-methane gas mixture similar to Titan’s atmosphere into a collection of nitrogen-containing organic molecules by irradiating the gas with high-energy ultraviolet light. The laboratory set-up was designed to mimic how solar radiation affects Titan’s atmosphere.

Most of the nitrogen simply formed solid compounds directly, rather than gaseous ones, explains Smith, whereas previous theories suggested that nitrogen would move from gaseous compounds to solid ones in stepwise process. But, those settling particles may not contain nitrogen at all. If some of the particles are the same nitrogen-containing organic molecules created by the UA team in the laboratory then it would suggest that conditions conducive to life might just exist on Titan, Smith says.

These and other laboratory observations help scientists planning future space missions to decide on what to look for on other worlds that might hint at life and what instruments should be developed to help in the search.

Links

Proc Natl Acad Sci, 2010, online
Mark A. Smith homepage
UA lunar and planetary laboratory