A Marvellous Month of Science

fungusFungal extracts prevent hepatitis C virus infection

Hepatitis C virus (HCV) is a huge cause of liver cancer, but current treatments are very expensive and not that great. Since HCV is a cunning little virus capable of quickly evolving drug resistance, simultaneously attacking it at several key points during its life cycle has the best chance of resolving infection. Researchers in Japan have now created and screened a library of 300 natural drugs isolated from fungi found on seaweed, mosses and other plants, and tested their ability to shut down HCV infection. One of their best hits, sulochrin, repelled several strains of hepatitis C virus, and was free from any toxic side effects. When they combined sulochrin with the traditional HCV drug, telaprevir, results were even better. Although any potential off-target effects of sulochrin still have to be ruled out, this research highlights that the natural world is a tremendously rich source of new drugs that should continue to be mined.

unwindingUnwinding shielded DNA attacks the root cause of prostate cancer

Most organs in the human body, including the prostate gland, contain a tiny population of stem cells that replace old defunct cells with shiny new ones. If these stem cells get damaged, they can become carcinogenic machines, dividing uncontrollably to form a tumour. Such cancer stem cells are thought to be the driving force that creates prostate tumours. Cancer stem cells are very difficult to kill, since they have excellent inbuilt safety features, one of which is very tightly coiled DNA that rebuffs normal treatments. Researchers at the University of York have now shown that treating prostate cancer stem cells with drugs that unwind and relax DNA sensitises them to common chemotherapies, allowing them to be destroyed and ultimately preventing tumour relapse.

Chilly temperatures help cancers to grow

7041602511_b7b65fc443_bAt low temperatures the human body has a hard time, entering a state of thermal stress  where only the most vital systems, like the brain, are left switched on. Now, a paper published in PNAS suggests that cold has yet another disadvantage – it changes the way cancer cells grow and spread, at least in mice. Mice living in a relatively cold environment (around 22°C) had cancers that grew more quickly and aggressively than mice living at a nice thermally comfortable temperature (around 30°C). Both the cold and the comfortable mice had the same numbers of potential cancer-fighting immune T cells when they were healthy, but when they got sick, the T cells in the comfortable mice were quicker and better at burrowing into the tumour to attack it. They also secreted more cancer-fighting substances than the cells from cold mice. In the tumours of cold mice, there were greater numbers of suppressive cells capable of shutting down normal immune responses. Cold temperatures, then, shifted the body’s response from fighting the tumour to accepting it. This suggests that the benefits of heat therapy for cancer may have been largely overlooked. Adapted from an article originally published on The Conversation.

HSVCommon chemotherapy drug helps oncolytic viruses kill tumours

There is a lot of excitement in the world of cancer immunotherapy over the potential utility of oncolytic viruses – that is, viruses that specifically infect and destroy cancer cells with the help of the immune system. Since a tumour is essentially a big chunk of overgrown tissue, the immune system often continues to see it as a normal part of the body (although sometimes, the sneaky tumour simply makes itself invisible to the immune system). Even after immune-activating oncolytic virus treatment, properly re-educating the immune system to see the tumour as a malignant intruder is a very difficult process. Researchers at McMaster Immunology Research Centre now show that administering an oncolytic virus together with a chemotherapy drug that triggers the immune system as it kills cancer cells finally allows the tumour to be recognised as a threat. Once that biological brake has been removed, cancer-fighting immune cells can pour into the tumour and secrete cancer-busting substances. Such exciting new combination therapies can help retrain the immune system to identify developing malignant disease.

Originally published on Scizzle.

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Chilly temperatures help cancers grow

7041602511_b7b65fc443_bAt low temperatures, the human body has a hard time. As the cold sets in, blood vessels constrict to maintain heat and some body parts – like fingers and toes – begin to suffer. Metabolism ramps up to fight the cold and shivering sets in. As these conditions continue, everything becomes sluggish as the cells of your body do not work as well. The body enters a state of thermal stress and only the most vital systems, like the brain, are left switched on.

Now, in a paper just published in the Proceedings of the National Academy of Sciences, Elizabeth Repasky at Roswell Park Cancer Institute in the US and colleagues suggest that cold has yet another disadvantage – it changes the way cancer cells grow and spread, at least in mice. This raises interesting questions about cancer therapies and many cancer studies, which tend to use mice as animal models.

Repasky found that mice living in a relatively cold environment (around 22°C) had cancers that grew more quickly and aggressively than mice living at a nice thermally comfortable temperature (around 30°C). A cold environment boosted the growth of several different types of cancer, including breast, skin, colon, and pancreas.

It did not matter if mice had lived in the cold for a lifetime before they got cancer—a chilly exposure even after their cancer had become established still made their tumours grow more quickly.

The body’s anti-cancer responses are mostly driven by the immune system’s T cells, which recognise and destroy tumor cells based on the altered proteins they produce. Tumours often react to a T-cell attack by producing signals that trick the body into suppressing these immune cells. This battle continues until one side outpaces the other – a lot of anti-cancer treatments given in the clinic help to swing the balance in favour of the immune system.

Both the cold and the comfortable mice had the same numbers of potential cancer-fighting T cells when they were healthy. But the tumour-seeking T cells in the comfortable mice were quicker and better at burrowing into the tumour to attack it. They also secreted more cancer-fighting substances than the cells from cold mice.

In the tumours of cold mice, there were greater numbers of suppressive cells capable of shutting down normal immune responses. Cold temperatures, then, shifted the body’s response from fighting the tumour to accepting it.

Most animal research facilities follow the same housing guidelines, and thus keep mice at colder-than-comfortable temperatures. This could introduce a systemic bias to animal testing where studies are done in conditions that aren’t entirely relevant. For example, what if you were trying a therapy that boosted immune function but did it in mice whose immune function was naturally tamped down? You might see no effect, when it could still be a useful drug. In contrast, something that causes tumour DNA damage might not have the same problem.

Cancers are cold

When we feel cold, we engage in warming behaviours – turning the thermostat up a notch, or thriftily putting on an extra layer of clothes. Mice are exactly the same – if they feel cold, they move to a warmer spot. When healthy mice get to choose what temperature they want to hang out at, with options at 22, 28, 30, 34 or 38°C, they typically migrate into the comfortable 30°C room. Mice with tumours tend to choose the hottest 38°C room. Cancer patients also commonly report suffering deep chills, especially following treatment.

It’s possible that growing tumours may induce a cold stress that probably promotes their own survival. We do not know exactly how this works yet, but this research still has important implications for cancer patients and their treatments. Could administering cancer therapies in a sauna – like setting improve their tumour – fighting potential and slow cancer growth?

Such approaches have been tried in small trials for breast cancer, angiosarcoma and sarcoma. They show that increasing body temperature to a mild fever over the course of a few hours improves response rates to radiation therapy.

Without large-scale studies no firm conclusions can be drawn, but this evidence suggests that the benefits of heat therapy for cancer may have been overlooked. Perhaps it is time we paid heed to the words of the ancient Greek physician Hippocrates:

Those who cannot be cured by medicine can be cured by surgery. Those who cannot be cured by surgery can be cured by heat. Those who cannot be cured by heat are to be considered incurable.

Originally published on The Conversation UK.

Kokolusa, KM, Capitanoa, ML, Leea, CT, Enga, JWL, Waighta, JD, Hylandera, BL, Sexton, S, Hong, CC, Gordon, CJ, Abrams, SI, & Repasky, EA (2013). Baseline tumor growth and immune control in laboratory mice are significantly influenced by subthermoneutral housing temperature PNAS : 10.1073/pnas.1304291110

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Creepy crawly centipedes are a source of new high-strength painkillers

13161493I’m dreading the day I get knocked up, since I know that my incredibly low pain threshold will have trouble dealing with the crazy horror that is childbirth.

That’s why I was overjoyed to hear of some new research from Australia, where a new high-strength painkiller has been isolated from the venom of the Chinese red-headed centipede, Scolopendra subspinipes mutilans.

Scolopendra_subspinipes_mutilans_DSC_1438

In the insect world, centipedes are king of the hill – their venom is debilitating to their prey, helping them to capture fish, lizards, frogs and even small mammals.

Centipede venom is made up of a complex cocktail of proteins, each designed to disengage a particular biological pathway. Researchers isolated one of these proteins, µ-SLPTX-Ssm6a, and found that it blocked a specific pain receptor known as the voltage-gated sodium channel, Nav1.7.

For several types of chemical-, temperature- or acid-based pain, µ-SLPTX-Ssm6a provided better pain relief than the current gold standard, morphine. Happily, no side effects were observed.

So, µ-SLPTX-Ssm6a is a great new drug candidate for human pain relief. And since other beastie-derived venom proteins are already in clinical use – like PRIALT from the marine cone snail – µ-SLPTX-Ssm6a could make it to market before I find me a baby daddy.

Yang S, Xiao Y, Kang D, Liu J, Li Y, Undheim EA, Klint JK, Rong M, Lai R, & King GF (2013). Discovery of a selective NaV1.7 inhibitor from centipede venom with analgesic efficacy exceeding morphine in rodent pain models. Proceedings of the National Academy of Sciences of the United States of America, 110 (43), 17534-9 PMID: 24082113

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Pumping out Petrol with Bioengineered Bugs

petrol

One of the terribly tricky questions in this ol’ world of ours is how to sustain a species that likes to extract toxic crude oil from the ground and use it in a way that’s disturbingly damaging to the environment they live in.

But imagine how much closer we would be to a renewable energy revolution if instead of sucking fossil fuel out of the earth, there was an alternative way to satisfy our need for fuel.

Enter: microbes.

We’ve already created genetically engineered bacteria that produce diesel, but not our favourite fuel, petrol. The difficulty lies in convincing bacteria to produce the short-chain hydrocarbons that form part of the petrol cocktail, since they much prefer making longer chains.

Researchers in South Korea have now addressed this issue by creating two new strains of Escherichia coli bacteria. After engineering in lots of additional genetic hardware – including DNA from Clostridium, Arabidopsis and Acinetobacter species – they substantially bumped E.coli’s capacity to produce short-chain hydrocarbons.

The first strain, Gas-2, produces a steady stream of short-chain free fatty acids, which are intermediate products in the petrol creation process, while the second strain, Gas-3, churns out short-chain hydrocarbons (i.e. petrol) at a rate of 580 milligrams per litre.

This work represents an excellent new starter platform for the sustainable production of biofuels.

Choi YJ, & Lee SY (2013). Microbial production of short-chain alkanes. Nature, 502 (7472), 571-4 PMID: 24077097

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“Grape-like aromas” keep mosquitoes at bay

mosquito_terror_by_kittenmittenmuffin-d5bgh44The mosquito is my dad’s nemesis in the insect world. He will go to extraordinary lengths to secure his person from mosquito attack, roaming the corridors on night patrols and jamming mosquito repellent devices into every possible plug socket.

Such devices are usually based on the chemical, N, N-diethyl-meta-toluamide, or DEET. The problem with DEET is it’s expensive, it has nasty effects on our own skin and mosquitos are evolving resistance to it.

But replacing DEET has proven a tricky business, since we don’t really know exactly how it prevents mosquitoes zeroing in on their bloodbag human targets.

Until now.

A team of researchers from the University of California found that mosquito nerve cells in the antenna expressing the receptor Ir40a were crucial for the anti-DEET effect. When this receptor was blocked, mosquitoes became resistant to DEET – and in a nightmarish twist, some became more drawn to its scent.

They then used a computer algorithm to screen over 3000 “natural odours”, including extracts from plants, insects or vertebrates, and ones already approved for use in perfumes, cosmetics and food additives, for their predicted ability to block Ir40a receptors.

Three promising compounds with a “grape-like aroma”, plus a fourth that ants secrete to mark their trail, had strong effects on nerves expressing Ir40a and repelled mosquitos.

Since these compounds already have WHO and FDA approval, they are exciting new candidates for an improved class of bug repellents that could be speedily translated to market.

Kain, P, Boyle, SM, Tharadra, SK, Guda, T, Pham, C, Dahanukar, A, & Ray, A (2013). Odour receptors and neurons for DEET and new insect repellents Nature : 24089210

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