Posts Tagged ‘discovery’

Showcase of latest advances in medical imaging for revolutionary proton therapy cancer treatment

The University of Lincoln’s Professor Nigel Allinson MBE will deliver the keynote talk at the tenth International Conference on Position Sensitive Detectors. The conference, which takes place from 7th to 12th September 2014, features the latest developments in this field from leading researchers around the world.

Professor Allinson leads the pioneering PRaVDA (Proton Radiotherapy Verification and Dosimetry Applications) project. He and his multinational team are developing one of the most complex medical instruments ever imagined to improve the delivery of proton beam therapy in the treatment of cancer.

Proton beam therapy is a type of particle therapy that uses a beam of protons to irradiate diseased tissue. Proton beam therapy has the ability to deliver high doses of radiation directly to a tumour site with very little radiation being absorbed into healthy tissue.

PRaVDA, funded by a £1.6 million grant from the Wellcome Trust, will provide a unique instrument capable of producing real-time 3D images — a proton CT — of a patient, drawing data from the same protons used in the treatment itself.

The patent-pending technology, which uses detectors at the heart of the Large Hadron Collider at CERN alongside world-first radiation-hard CMOS imagers, will reduce dose uncertainties from several centimetres to just a few millimetres.

This promises to make proton therapy an option for thousands more cancer patients by reducing the risks of healthy tissue being damaged during treatment, particularly in vulnerable parts of the body such as the brain, eye and spinal cord.

Professor Allinson, who will also be talking about his research to prospective students at the University of Lincoln open day on Saturday, 20th September, said: “PRaVDA will ensure more difficult tumours will become treatable and more patients overall will be able to receive this revolutionary treatment.”

Other members of the PRaVDA team will also present their work at the conference, describing in more detail the high-speed tracking technology that can record the paths of individual protons as they enter and leave a patient. The team will also outline how they make and test the new detectors in PRaVDA to ensure they are resistant to the high levels of radiation present in proton therapy.

The researchers have just taken delivery of some of the technology which will lie at the heart of the system: two state-of-the-art custom integrated circuits (chips) which will underpin PRaVDA’s imaging capabilities.

One device is a radiation-hard CMOS imager, measuring 10cm x 6.5cm, and producing more than 1,500 images per second. The camera chip in a mainstream smartphone is a CMOS imager but PRaVDA’s chip is over 300 times larger and operates 50 times faster — the fastest large-area CMOS imager ever made. The completed PRaVDA instrument will contain 48 of these imagers, giving a total imaging area of nearly two-and-a-half square metres.

The second device is the read-out chip for the very high-speed strip detectors that track the passage of individual protons as they enter and exit a patient. This chip, called Rhea, converts the electric charge created by a passing proton into a digital signal with additional logic to provide accurate timing (to one hundredth of one millionth of a second) while preventing erroneous signals being recorded.

The strip detectors were designed at the University of Liverpool by the same team that developed detectors for the Large Hadron Collider at CERN, which led to the discovery of the Higgs Boson in 2013. Nearly 200 Rheas are used in the complete PRaVDA system.

PRaVDA’s industrial partner, ISDI LTD, designed both devices. Their testing was undertaken by the project’s second industrial partner, aSpect Systems GmbH, in Dresden, Germany.

source : http://www.sciencedaily.com/releases/2014/09/140904121147.htm

Understanding, improving body’s fight against pathogens

While they exist in small populations in humans, the large amounts of antibodies secreted by plasma cells make them key to the body’s immune system and its ability to defend itself against pathogens, such as bacteria and viruses. Proper maintenance of a pool of plasma cells is also critical for the establishment of lifelong immunity elicited by vaccination.

Dysregulation of plasma cell production and maintenance could lead to autoimmune diseases and multiple myeloma. Autoimmune diseases occur when the immune system does not distinguish between healthy tissue and antigens, which are found in pathogens. This results in expansion of plasma cells which produce excessive amounts of antibodies leading to destruction of one’s own healthy tissue. The discoveries by scientists in BTI’s Immunology Group have improved understanding of the mechanism by which plasma cells are developed from a major class of white blood cells called B cells.

For the first time, the molecule DOK3 was found to play an important role in formation of plasma cells. While calcium signalling typically controls a wide range of cellular processes that allow cells to adapt to changing environments, it was found to inhibit the expression of the membrane proteins essential for plasma cell formation. These membrane proteins include PDL1 and PDL2, and represent some of the key targets for the development of immunotherapy by pharmaceutical companies. DOK3 was able to promote the production of plasma cells by reducing the effects of calcium signalling on these membrane proteins. The absence of DOK3 would thus result in defective plasma cell formation.

In another study, BTI scientists discovered the importance of SHP1 signalling to the long term survival of plasma cells. While the molecule SHP1 has a proven role in prevention of autoimmune diseases, it was found that the absence of SHP1 would result in the failure of plasma cells to migrate from the spleen where they are generated to the bone marrow, a survival niche where they are able to survive for much longer periods. This could result in a reduction of the body’s immune response and thus, an increased susceptibility to infections and diseases. The scientists in this study also successfully rectified the defective immune response caused by an absence of SHP1 by applying antibody injections, which might advance the development of therapeutics. On the other hand, targeting SHP1 might be a strategy to treat multiple myeloma where the accumulation of cancerous plasma cells in the bone marrow survival niches is undesirable.

Findings hold potential for improved treatment

The discovery of these new targets for modulating the antibody response allows the development of novel therapeutic strategies for patients with autoimmune diseases and cancer.Understanding the mechanism that governs plasma cell differentiation is also critical for the optimal design of vaccines and adjuvants, which are added to vaccines to boost the body’s immune response.

Prof Lam Kong Peng, Executive Director of BTI, said, “These findings allow better understanding of plasma cells and their role in the immune system. The identification of these targets not only paves the way for development of therapeutics for those with autoimmune diseases and multiple myeloma, but also impacts the development of immunological agents for combating infections.”

source : http://www.sciencedaily.com/releases/2014/09/140902115036.htm

Study identifies protein that helps prevent active tuberculosis in infected patients

The discovery could help doctors identify people who are at the greatest risk for the highly contagious and potentially fatal lung disease, and it could point the way toward new treatment strategies for TB.

The study, conducted in partnership with researchers from Harvard University School of Public Health and the University of Michigan School of Medicine, was published in the Aug. 20 online edition of the journal Science Translational Medicine.

The findings underscore the importance of maintaining sufficient levels of vitamin D to effectively combat the pathogen that causes TB. The researchers found that the protective protein, interleukin-32, can induce the killing of the TB bacterium only in the presence of sufficient levels of vitamin D.

An estimated one-third of the world’s population is infected with tuberculosis, but the disease is latent in 90 to 95 percent of infected people, meaning that they experience no symptoms and are not contagious. Interleukin-32 contributes to maintaining that latent state and preventing active infection. In 2012, nearly 9 million people worldwide became sick with TB and there were 1.3 million TB-related deaths, according to the U.S. Centers for Disease Control and Prevention.

A new urgency for developing new approaches to identify individuals at risk, maintain immunity and treat active disease has arisen in recent years as TB has re-emerged as a global health threat — thanks in part to the rise of extremely drug-resistant bacteria. “Until now, there had been no way to predict, based on biological factors, why latently infected individuals do not develop active tuberculosis,” said Dennis Montoya, a postdoctoral scholar in the division of dermatology at the David Geffen School of Medicine at UCLA and the study’s lead author. “We were surprised to find many differences between people with latent TB and healthy people, suggesting that people with latent TB may have activated immune systems that are protecting them from developing active infection.” In people with active TB, the disease-causing bacteria have overcome the defenses of the immune system, causing symptoms to develop in the lungs. Previous studies have focused on finding biological markers of disease progression in those patients. The new study, however, was the first to look for markers of protection in the blood of people with latent TB — those who are infected but have not developed symptoms.

The researchers analyzed gene expression profiles of hundreds of TB patients in four countries, as well as evaluating genes from activated immune cells shown in the laboratory to have the ability to kill the TB bacteria. They discovered that in people who were infected with TB but had higher levels of interleukin-32 (IL-32), the disease was more likely to be latent, and that — in laboratory experiments — IL-32 was able to stimulate the immune system to kill TB-causing bacteria, but only in the presence of sufficient vitamin D levels.

Vitamin D is produced in the skin upon exposure to sunlight, but approximately one-third of American adults — particularly members of ethnic minorities with darker-pigmented skin and lighter-skinned people who receive minimal sun exposure — lack sufficient levels of vitamin D, and vitamin D deficiency has been found to be associated with a higher risk for active TB.

“When vitamin D levels were low, IL-32 was not able to kill the bacteria,” said Dr. Robert Modlin, the Klein Professor of Dermatology at UCLA and the study’s senior author. “However, if we simulated the effect of supplementing individuals by adding vitamin D to the culture of the activated immune cells that had low vitamin D levels, IL-32 regained its ability to kill. Our findings suggest that raising standards for daily intake of vitamin D could help to protect against a TB pandemic.”

Further studies are needed to determine if vitamin D supplementation helps prevent TB. But Modlin, a dermatologist, favors oral supplementation rather than increased sun exposure, which can increase the risk of skin cancer.

Although TB remains a leading killer in many parts of the world, the incidence of the disease has been declining in the U.S. since a resurgence that peaked in 1992, according to the CDC. A total of 9,945 cases were reported in 2012, and 569 people died from the disease in 2010, the most recent years for which U.S. data are available. In the U.S., unlike in many poorer countries, patients known to have latent TB infections are typically treated with antibiotics to prevent progression to the active disease. But strains of the tuberculosis bacteria are becoming resistant to the antibiotic drugs, increasing the threat of a multidrug-resistant TB pandemic that could affect the U.S.

“Our current strategy of antibiotic therapy, as well as methods of identifying which patients will develop severe disease, have remained essentially unchanged for decades,” said Harvard’s Barry Bloom, the study’s co-author. “Our findings of specific markers in the blood that can tell us which people are at risk can help countries focus limited resources on patients who have lower levels of this protein. In addition, this may point the way to new treatments for a disease that greatly needs them.”

The research builds on the team’s previous work that found that vitamin D is important for killing TB bacteria.

source : http://www.sciencedaily.com/releases/2014/08/140820164311.htm