Searching for magic bullet against cancer caused by asbestos: One step closer?

Jan. 17, 2014 — Mesothelioma is a very aggressive cancer associated with asbestos exposure, which is usually diagnosed in an advanced stage. So far no therapeutic strategy has proven effective against this deadly cancer and the prognosis remains very poor with only few exceptions.

In December, the research team of Antonio Giordano, a pathologist, Director and Founder of the Sbarro Health Research Organization in Philadelphia, PA, and Professor of Pathology and Oncology at the University of Siena, Italy, published two separate studies aiming to address the urgent need to identify possible new methods for mesothelioma treatment.

In the first study, published in the scientific journal Cell Cycle, Giordano's researchers tested on mesothelioma cells the effect of two drugs designed to reactivate the p53 protein, one of the most important 'tumor suppressors', which is turned off in most human cancers. "In mesothelioma, although p53 is rarely mutated, it is inactivated by alterations in its pathway," says Francesca Pentimalli of the National Cancer Institute of Naples, Italy, lead author of the study. Both of the drugs used in the study target p53, but with different mechanisms of action. One in particular, called RITA, proved to be very toxic. Specifically, RITA caused mesothelioma cells, and not 'healthy' cells, to undergo apoptosis -- a type of programmed cell death that occurs through the activation of a specific 'cascade' of events.

"The ability of RITA to induce apoptosis is remarkable considering that mesothelioma is very refractory to this process. In fact the most aggressive and rare variant, sarcomatoid mesothelioma, did not respond to the treatment probably because of its intrinsically high levels of molecules acting as inhibitors of this process" says Alfredo Budillon, Head of the Experimental Pharmacology Unit of the National Cancer Institute of Naples and coauthor of the study. "It remains to be seen whether the combination of RITA with other activators of apoptosis can achieve efficacy also against the more aggressive cases."

Furthermore, challenging mesothelioma cells with RITA worked in synergy with the chemotherapy drug cisplatin, which is the mainstay of treatment for this disease, suggesting that its use in a clinical setting could possibly help to reduce the required doses and the side effects of chemotherapy, thereby improving patients' quality of life.

The second study, published online in Cancer Biology and Therapy and led by Paola Indovina of the University of Siena and the Sbarro Institute for Cancer Research and Molecular Medicine, Temple University in Philadelphia, was designed along the same lines as the first study. In the second study, the authors tested, for the first time in mesothelioma, a new drug called MK-1775 in combination with cisplatin. MK-1775 is a selective inhibitor of WEE1, a protein that is crucial in activating a 'checkpoint' for the repair of damaged DNA before the cell starts its division process. The rationale for this strategy is based on the fact that many cancer cells, especially those with non-functional p53, rely on WEE1 to stall cell division and allow cells to repair the damage induced by genotoxic agents, such as many chemotherapeutic drugs, including cisplatin. WEE1 inhibition limits the time available for repair and, therefore, sensitizes cancer cells to DNA-damaging agents. Indeed, inhibiting WEE1 with MK-1775 selectively sensitized mesothelioma cells to the genotoxic action of cisplatin by preventing checkpoint activation and forcing the cells to divide despite the damage, thus triggering apoptosis.

"Overall our studies are aimed at identifying promising new molecular therapies against mesothelioma that hold the potential for clinical use in the near future. MK-1775, for example, is already being utilized in clinical trials for other types of tumors in the United States," Giordano concludes.

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Human robot getting closer: iCub robot must learn from its experiences

Sep. 27, 2013 — A robot that feels, sees and, in particular, thinks and learns like us. It still seems like science fiction, but if it's up to UT researcher Frank van der Velde, it won't be. In his work he wants to implement the cognitive process of the human brain in robots. The research should lead to the arrival of the latest version of the iCub robot in Twente. This human robot (humanoid) blurs the boundaries between robot and human.

Decades of scientific research into cognitive psychology and the brain have given us knowledge about language, memory, motor skills and perception. We can now use that knowledge in robots, but Frank van der Velde's research goes even further. "The application of cognition in technical systems should also mean that the robot learns from its experiences and the actions it performs. A simple example: a robot that spills too much when pouring a cup of coffee can then learn how it should be done."

Possible first iCub in the Netherlands

The arrival of the iCub robot at the University of Twente should signify the next step in this research. Van der Velde submitted an application together with other UT researchers Stefano Stramigioli, Vanessa Evers, Dirk Heylen and Richard van Wezel, all active in the robotics and cognitive research. At the moment, twenty European laboratories have an iCub, which was developed in Italy (thanks to a European FP7 grant for the IIT). The Netherlands is still missing from the list. Moreover, a newer version is currently being developed, with for example haptic sensors. In February it will be announced whether the robotics club will actually bring the latest iCub to the UT. The robot costs a quarter of a million Euros and NWO (Netherlands Organisation for Scientific Research) will reimburse 75% of the costs. Then the TNO (Netherlands Organisation for Applied Scientific Research) and the universities of Groningen, Nijmegen, Delft and Eindhoven can also make use of it. Within the UT, the iCub can be deployed in different laboratories thanks to a special transport system.

Robot guide dog

The possibilities are endless, according to Van der Velde. "The new iCub has a skin and fingers that have a much better sense of touch and can feel strength. That makes interaction with humans much more natural. We want to ensure that this robot continues to learn and understands how people function. This research ensures, for example, that robots actually gather knowledge by focusing on certain objects or persons. In areas of application like healthcare and nursing, such robots can play an important role. A good example would be that in ten years' time you see a blind person walking with a robot guide dog."

Nano-neural circuits

A recent line of research that is in line with this profile is the development of electronic circuits that resemble a web of neurons in the human brain. Contacts have already been made to start this research in Twente. In the iCub robot, this can for example be used for the robot's visual perception. This requires a lot of relatively simple operations that must all be performed in parallel. This takes a lot of time and energy in the current systems. With electronic circuits in the form of a web of nerve cells this is much easier.

"These connections are only possible at the nanoscale, that is to say the scale at which the material is only a few atoms thick. In combination with the iCub robot, it can be investigated how the experiences of the robot are recorded in such materials and how the robot is controlled by nano-neural circuitry. The bottleneck of the existing technical systems is often the energy consumption and the size. The limits of Moore's Law, the proposition that the number of transistors in a circuit doubles every two years through technological advances, are reached. In this area we are therefore also on the verge of many new applications."

Video: http://www.youtube.com/watch?v=ZcTwO2dpX8A

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Scientists closer to universal flu vaccine after pandemic 'natural experiment'

Sep. 22, 2013 — Scientists have moved closer to developing a universal flu vaccine after using the 2009 pandemic as a natural experiment to study why some people seem to resist severe illness.

Researchers at Imperial College London asked volunteers to donate blood samples just as the swine flu pandemic was getting underway and report any symptoms they experienced over the next two flu seasons.

They found that those who avoided severe illness had more CD8 T cells, a type of virus-killing immune cell, in their blood at the start of the pandemic.

They believe a vaccine that stimulates the body to produce more of these cells could be effective at preventing flu viruses, including new strains that cross into humans from birds and pigs, from causing serious disease.

The findings are published in Nature Medicine.

Professor Ajit Lalvani from the National Heart and Lung Institute at Imperial College London, who led the study, said: "New strains of flu are continuously emerging, some of which are deadly, and so the Holy Grail is to create a universal vaccine that would be effective against all strains of flu."

Today's flu vaccines make the immune system produce antibodies that recognise structures on the surface of the virus to prevent infection with the most prevalent circulating strains. But they are usually one step behind as they have to be changed each year as new viruses with different surface structures evolve.

Previously, experimental models had suggested that T cells may protect against flu symptoms but until now this idea has not been tested in humans during a pandemic.

Professor Lalvani's team rapidly recruited 342 staff and students at Imperial to take part in their study in autumn 2009. The volunteers donated blood samples and were given nasal swabs. They were sent emails every three weeks asking them to fill in a survey about their health. If they experienced flu symptoms, they took a nasal swab and sent it back to the lab.

They found that those who fell more severely ill with flu had fewer CD8 T cells in their blood, and those who caught flu but had no symptoms or only mild symptoms had more of these cells.

Professor Lalvani said, "The immune system produces these CD8 T cells in response to usual seasonal flu. Unlike antibodies, they target the core of the virus, which doesn't change, even in new pandemic strains. The 2009 pandemic provided a unique natural experiment to test whether T cells could recognise, and protect us against, new strains that we haven't encountered before and to which we lack antibodies.

"Our findings suggest that by making the body produce more of this specific type of CD8 T cell, you can protect people against symptomatic illness. This provides the blueprint for developing a universal flu vaccine.

"We already know how to stimulate the immune system to make CD8 T cells by vaccination. Now that we know these T cells may protect, we can design a vaccine to prevent people getting symptoms and transmitting infection to others. This could curb seasonal flu annually and protect people against future pandemics."

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