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

Biofilters cut old landfill carbon footprint

Researchers in the US are testing biofilter systems as a viable alternative to releasing methane from passive landfill vents into the atmosphere. The technology could reduce the overall impact of old landfills on global warming. Details are reported in the current issue of the International Journal of Environmental Engineering.

Organic matter rotting in smaller, old landfill sites generates a slow trickle of the potent greenhouse gas, methane, into the atmosphere, amounting to just 2 or 3 kilograms per day per vent. In contrast to controlled methane generate for biofuel from modern, managed landfills, tapping this slow stream of the gas is not viable technologically or economically. However, methane has an infrared activity 21 times greater than carbon dioxide and so represents an important anthropogenic source of this greenhouse gas when attempting to balance the climate change books. Indeed, landfills contribute 12% of worldwide anthropogenic methane emissions due to the decomposition of organic waste.

Old landfills typically have passive gas vents. Methane is simply released into the atmosphere from these vents, or if the rate of emission is high enough it can be burned, or flared. According to Tarek Abichou and Jeffery Chanton of the Florida State University, Jose Morales of Environmental and Geotechnical Specialists, Inc., Tallahassee, Florida and Lei Yuan of Geosyntec Consultants in Columbia, Maryland, methane oxidation has recently been viewed as a more benign alternative to venting or flaring of landfill methane.

The researchers tested two biofilter designs capable of oxidizing methane gas to carbon dioxide and water. Both are packed with so-called methanotrophic bacteria, microbes that digest methane. They found that the radial biofilter design gave a much higher methane oxidation rate than a vertical biofilter. The higher surface area exposed to methane flow led to greater oxygen penetration into the biofilters, essential for microbial digestion. The radial biofilter has a surface area of well over 1.2 square meters whereas the vertical biofilter amounts to just 0.3 square meters area.

The team also found that the average percent oxidation rate of 20% and higher for the radial biofilter was possible when the air temperature was 20 to 36 Celsius, indicating the optimal soil temperature for methanotrophic bacteria to oxidize methane. Vertical biofilters averaged a little over 12% oxidation.

Abichou, T., Yuan, L., Chanton, J., & Morales, J. (2011). Mitigating methane emissions from passive landfill vents: a viable option for older closed landfills International Journal of Environmental Engineering, 3 (3/4) DOI: 10.1504/IJEE.2011.041354