Posts Tagged ‘system’

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

One-two punch for brain tumors? New clinical trial opens

The experimental approach, based on U-M research, delivers two different genes directly into the brains of patients following the operation to remove the bulk of their tumors.

The idea: trigger immune activity within the brain itself to kill remaining tumor cells — the ones neurosurgeons can’t take out, which make this type of tumor so dangerous.

It’s the first time this gene therapy approach is being tried in humans, after more than a decade of research in experimental models.

One of the genes is designed to kill tumor cells directly, and is turned on when the patient takes a certain drug. The other gene spurs the body’s own immune system to attack remaining cancer cells. Both are delivered into brain cells via a harmless virus.

The Phase I clinical trial has already enrolled two patients who have tolerated the gene delivery without complications. All patients in the study must have a presumptive diagnosis of WHO grade 3 or 4 malignant primary glioma, such as glioblastoma multiforme; patients must not have been treated yet by any therapy. They must also meet other criteria for inclusion in the trial.

More patients will be able to enroll at a pace of about one every three weeks, through a careful selection process. In addition to surgery and gene therapy at U-M, each will receive standard chemotherapy and radiation therapy as well as follow-up assessments for up to two years.

“We’re very pleased to see our years of research lead to a clinical trial, because based on our prior work we believe this combination of cell-killing and immune-stimulating approaches holds important promise,” says principal investigator Pedro Lowenstein, M.D., Ph.D., the U-M Medical School Department of Neurosurgery professor who has co-led the basic research effort to develop and test the strategy.

Co-leader Maria Castro, Ph.D., notes that the patients who agree to take part in the Phase I trial will be the first in the world to help establish the safety of the approach in humans. “Without them, and without our partners on the U-M Neurosurgery team, and donors to the Phase One Foundation that support our work, we wouldn’t be able to take this important step in testing this novel therapeutic approach.”

For more about the trial, visit http://umhealth.me/gliomatrial or call 1-800-865-1125.

source : http://www.sciencedaily.com/releases/2014/09/140902143230.htm

Being overweight causes hazardous inflammations

“We believe that there is a connection between metabolism, inflammation, heart attack and stroke,” says Bente Halvorsen, professor at the Research Institute for Internal Medicine, University of Oslo, Norway. Together with the research group’s leader, Pål Aukrust, who last year received the university’s research award for his work on inflammatory diseases, and researcher Arne Yndestad, she has looked deeply into the molecular explanation of why overweight is harmful. “With this new knowledge, we can better understand why too much food can cause such serious diseases as heart attack, stroke, cancer and chronic intestinal inflammation.”

We eat too much

Malnutrition and insufficient nutrition lower the immune response, and this increases the risk of infections. If the immune defense system functioned normally, the body would respond with an inflammation to rid itself of the infection. When the immune defense system is impaired, the body is unable to defend itself through inflammation.

Overeating increases the immune response. This increased immune response causes the body to generate excessive inflammation, which may lead to a number of chronic diseases.

“It is therefore important to keep a balance. Too little and too much nutrition may both upset the immune defense system and increase the risk of disease.”

A number of diseases are caused by inflammation. Arthritis is a chronic inflammatory disease. Heart attack is an example of a disease that causes an acute and powerful inflammatory reaction.

“We can reduce the inflammatory reaction by losing weight. Some people risk never getting rid of the inflammation. We have attempted to understand what is needed to reduce the inflammatory reaction without having to lose weight,” Halvorsen explains.

Unfortunately, storage of energy causes an inflammatory reaction. The explanation lies in the close connection between the body’s immune system, energy conversion and the way in which we store energy. It can all be explained in terms of evolution. In our ancestors many hundred million years ago, this was all concentrated in one single organ, like in the modern-day fruit fly. Even though in humans this task is divided among three organs — the fatty tissue that stores energy, the liver that converts energy and the immune system — these organs still communicate closely with each other.

Evolutionarily speaking, humans are not made to eat so much on the contrary; they are intended to toil for their food.

“Mankind’s great challenge has consisted in obtaining sufficient food and surviving infections. Today, we rarely die of infections, but on the other hand we eat too much,” says Arne Yndestad.

Damage to the powerhouse in the cells

The researchers believe that overeating may cause stress to the mitochondria. The mitochondria are the cells’ powerhouses, converting fatty acids to energy.

Evolutionary biologists believe that mitochondria were bacteria that as life has developed have become an integrated part of our cells. The immune system may nevertheless perceive the mitochondria as foreign bodies. Much immunological research therefore focuses on the mitochondria.

When fatty acids accumulate in the cells, the mitochondria become stressed and gradually also damaged.

“When the cells receive excessive energy, the system starts to falter, and the engine may stall. Too much fatty acid causes an oxidative stress in the cells. We believe that long-term stress on the mitochondria may cause metaflammation. A metaflammation is a low-grade chronic inflammation over many years, and unfortunately it’s a condition that’s difficult to detect,” says Yndestad.

The body has its own defense system, called autophagy, which should eliminate damaged mitochondria. When we overeat, free fatty acids accumulate in the cells. This stresses the mitochondria. The stress in the cells causes damage to the mechanism that should eliminate the mitochondria.

When damaged mitochondria accumulate, the immune response is activated. This immune response is exactly what causes the inflammation.

Key signal molecules have been found

The UiO researchers, who also work at the new K.G. Jebsen Inflammation Research Centre, have studied some of the signal molecules inside the cells that trigger the inflammatory reaction. In other words, they have found one element of the energy conversion that may explain what happens when the mitochondria are dealing with the fatty acids. The special element, which is also an enzyme, has previously been studied in stroke patients.

“We believe that this enzyme can be regulated by overnutrition and that it is a key constituent in the inflammatory reaction. We have found that the plaque in the arteries of patients with arteriosclerosis contained a lot of this enzyme. When the plaque bursts, the patient may suffer a stroke,” Halvorsen points out.

In trials with mice, the researchers have tested what happens when the amount of this special enzyme is increased. It reduced the degree of arteriosclerosis.

Strengthening the theory

Their theory was strengthened when they studied how the absence of inflammasomes had an effect on heart function. Inflammasomes are part of the intra-cellular immune defense system.

“When the cells received excessive amounts of fatty acids, the inflammasomes were activated, causing an inflammation.”

Mice with heart attacks functioned better when the inflammasomes were removed.

“So this is about restoring the balance in the immune defense system,” says Yndestad .

A correlation with cancer

The researchers believe that their new discovery may also be a key mechanism in the development of cancer.

“Cancer cells need access to a lot of energy to divide. The cellular stress may transform cells to cancer. Studies of overweight may therefore give us a better understanding of cancer,” Halvorsen explains.

One who is particularly interested in this research is Professor Kristin Austlid Taskén at the Institute for Cancer Research.

“People who are overweight more often develop an aggressive variant of prostate cancer. Although the connection between overweight and cancer is well known, however, little is known about the mechanisms involved” Taskén says.

Her specialty is prostate cancer, a disease that strikes 5000 Norwegians each year.

“Since this is the most common form of cancer among men, it is essential to obtain more knowledge about the way in which overweight affects the metabolism of the cancer cells and leads to aggressive prostate cancer. For the cancer cells to be able to divide rapidly, they make use of new metabolic pathways that are quite unknown to us today. It is therefore useful to have more knowledge that can help us find new drugs that can dispose of the cancer cells,” Taskén points out to the research magazine Apollon.

source : http://www.sciencedaily.com/releases/2014/08/140825084836.htm