Spinning Out In Control

In Signs of Resistance and Seeing the Invisible we emphasized two things well known to the interested, namely that most cancer deaths occur because cells spread from the original (primary) to secondary sites (metastases) where they are very difficult to treat, and that this places massive importance on early detection. Many will also be familiar with the currently used methods for tumor detection – X-ray based imaging (as in mammography and CT scans) and PET that detects injected radioactive tracers. The problem is that these are not sensitive enough to detect growths smaller than about 1 cm in diameter – and by that point there are several hundred million cells in the tumor and some may already have metastasized.

Tumor cells spread around the body by detaching from the primary and getting into the circulatory system and it’s beginning to look as though quite literally tapping into the circulation may revolutionize cancer detection. Seeing the Invisible showed how silicon chip technology can be used to retrieve circulating tumor cells (CTCs) by getting them to stick to targets anchored in a flow cell. Although this is hugely promising, another very recent advance may be even more effective. This uses centrifugal force to separate cells in blood on the basis of their size – that’s the one that pushes outwards on objects rotating about an axis. Because force is proportional to mass and tumor cells are larger than red blood cells and most white cells, this effect can be used to extract CTCs from fluid being pumped around a spiral microchannel. The spirals are made from a silicon-based polymer (the same stuff that’s used for contact lenses) stuck on glass slides and they have two outlet channels. Their shape creates two-counter rotating vortices in the fluid that exert a drag force on the cells so that bigger (heavier) tumor cells can be selectively directed to one of the outlets. Typically red blood cells are about 6 microns (one-millionth of a metre), white cells 8-14 microns and CTCs 16-25 microns in diameter.

The vortices are named after a Cambridge chappie, William Dean, who worked on flow patterns in curved pipes and channels and you can look up Dean vortices on the internet for images of these in action.

MCF7s right, rest left

In this picture of the two exits from a spiral microchannel breast cancer cells are carried to the right (yellow arrows) whilst all the other types of blood cell funnel left.

This method appears to be remarkably efficient in that over 90% of tumor cells (10-100 cells per ml of blood) can be separated from 99.99% of red cells (5,000,000 per ml) and 99.6% of white cells (10,000 per ml).

References

Hou, H.W., Warkiani, M. E., Khoo, B.L., Li, Z.R., Soo, R.A., Tan, D.S.-W., Lim, W.-T., Bhagat, A.A.S., and Lim, C.T. (2013). Isolation and retrieval of circulating tumor cells using centrifugal forces. Scientific Reports 3, Article Number: 1259. DOI: 10.1038/srep01259.

Bhagat, A.A.S. et al., 15th International Conference on Miniaturized Systems for Chemistry and Life Sciences October 2-6, 2011, Seattle, Washington, USA

Delay Olympics for eight years, says biochemist

No he didn’t because that would just be silly wouldn’t it? What my colleague Chris Cooper from the University of Essex was reported as saying by The Independent was “Delay awarding London 2012 Olympic medals for eight years” because he thinks it will take that long for drug tests to separate who was playing the game (cricket, obviously) from the cheats – the word taken from Chris’s book Run Swim, Throw, Cheat.

The current front-runner in the game of Beat the Biochemists appears to be erythropoietin (EPO) – a natural hormone that makes us produce more red blood cells. That’s handy if you go in for endurance events (like surviving t.v. coverage of the Olympics). The Boffins went 1 – 0 up recently by coming up with a test that picks up EPO after it’s been injected.

You don’t know how lucky you are!

In the second leg the Scoundrels have hit back with fiendish cunning. A key factor that regulates whether we make EPO is oxygen availability. Lower oxygen means more red cells needed. But for that to happen there has to be a molecular messenger that can sense oxygen levels. There is: it’s a protein called hypoxia-inducible factor (HIF, of course) that under normal conditions gets broken down very quickly – by a process that needs oxygen. So when oxygen drops HIF lasts longer, makes more EPO and that makes more red cells. The crafty bit is finding another molecule that stabilizes HIF – in effect, enables it to survive even when there’s plenty of oxygen. HIF stabilizers are potentially important in treating some diseases and they’re just the ticket if you want to cheat in the 5,000 km bog snorkel.

There’s a bit of a concern because HIFs play an important role in helping cancers to grow so, adding that to the stress of wondering if you’re going to be nicked, it’s all going to be a bit of a strain for any ‘athletes’ who succumb to temptation. But there’s a time-honoured way of dealing with stress and this isn’t the moment to spoil the ship. A pack a day should do the trick.

Sorted. It’s all systems go for gold in the true Olympian spirit, Lucky Strikes in one pocket, HIF stabilizers in the other, morals in the changing room. The Boffins are scuppered, at least until they can find a way of detecting the invisible EPO driver, unless of course the fags give things away. What the score-line will be when we hear the merciful blast of the final whistle on 12th August is anyone’s guess – but for once I wouldn’t bet on the Boffins.

So who was the idiot responsible for the title of this piece? What could have possessed him? I have no idea but here’s a guess. What if he thought: let’s ban the Olympics for two rounds – and come 2020 everyone will say “Gee, what a great eight years we’ve had with none of the colossal waste of money on these staggeringly over-hyped, extraordinarily tedious and somewhat malodorous events. Let’s not bother any more.” Give that man a medal – without delay!

Reference

http://www.independent.co.uk/sport/olympics/news/delay-awarding-london-2012-olympic-medals-for-eight-years-says-biochemist-7917937.html