A group of 15-16 year old students have been reporting directly to the UK government, (Tuesday 30th June), on their proposals for how nanotechnology could be used to help meet the future needs of the healthcare sector.

During a two week placement period at the Science and Technology Facilities Council’s (STFC’s) Rutherford Appleton Laboratory the A-level and GCSE students have been working on the ‘Nanotechnology in Healthcare’ project which involves researching the key areas in the health sector that need addressing, the technologies currently available to do this and how the UK can play a role. It’s being sponsored by STFC’s Futures Programme, which was set up in response to the government’s Grand Challenges, which are a set of key priorities set up to respond to the future demands of society.

The students are gathering information from across Europe to see what’s currently happening in nanotechnology, with the ultimate aim of forming an international collaboration to move towards a common goal. Countries would work together with the joint aim of meeting future health sector needs, with a particular focus on the treatment of diabetes, cancer and cardiology.

The students are leading the project themselves, with each group having a Team leader and an Executive Officer nominated by fellow students. They have the support of STFC research and technical staff, but are very much encouraged to work on their own initiative. The same project was run last year, but with a focus on space instead of healthcare.

On Tuesday 30th June the students presented their current findings, to members of the government’s ‘think tank’ on science and technology; ‘Foresight’, which uses the best evidence from science and other areas to provide guidance for future policies.

“I’m a little bit proud that we’ve managed to take in so much new information and that we get to talk to some quite important people to show them what we’ve spent our time doing. The whole project’s given us a real taste of working in an adult environment and taught us to work in a team”, said 16 year old Caroline Mace` from St Helen and St Katharine school in Abingdon.

Gareth Derbyshire, from STFC’s Futures Programme said; “These students are capable of having a real influence over the way science is developed in the future to meet the ever changing demands of the health service. It is their future in their own hands. We hope the successful completion of these projects will give the students the confidence and inspiration to go on to become scientists who can really make a difference”.

The students will present the final results of their projects to parents and lecturers in a special assembly at the STFC’s Rutherford Appleton Laboratory (RAL) in Oxfordshire on Friday (4th July).

Notes

The ‘Nanotechnology in Healthcare’ project is being sponsored by STFC’s Futures programme, an initiative set up in response to the Treasury’s Grand Challenges, which are designed to respond to the future demands of society. The four key priority areas being focused on by Futures are energy, security, healthcare and environment.

The students are all aged 15 and 16 doing either A-levels or GCSEs. They come from St Helen and St Katharine, Aylesbury Grammar, The European school in Culham, Oundle school in Peterborough, King Edward VI Grammar in Chelmsford, Nonsuch highschool in Cheam and Sherfield school in Sherfield.

The presentations at RAL will take place at 4pm on Friday 4th July.

RAL offers one or two week work placements to over 60 students each year, many from local schools and mostly for year 10 students. RAL also has many activities for students and teachers including visits, lectures, events and teacher development courses. For further information please contact Caroline Callard on 01235 445789.

Foresight

The aim of the government’s Foresight programme is to provide visions of the future using robust science to be used by policymakers to inform government policy and strategy, and to improve how science and technology are used within Government and by society.

http://www.foresight.gov.uk/About/index.asp

Science and Technology Facilities Council

The Science and Technology Facilities Council ensures the UK retains its leading place on the world stage by delivering world-class science; accessing and hosting international facilities; developing innovative technologies; and increasing the socio-economic impact of its research through effective knowledge exchange partnerships.

The Council has a broad science portfolio including Astronomy, Particle Physics, Particle Astrophysics, Nuclear Physics, Space Science, Synchrotron Radiation, Neutron Sources and High Power Lasers. In addition the Council manages and operates three internationally renowned laboratories:

- The Rutherford Appleton Laboratory, Oxfordshire
- The Daresbury Laboratory, Cheshire
- The UK Astronomy Technology Centre, Edinburgh

The Council gives researchers access to world-class facilities and funds the UK membership of international bodies such as the European Laboratory for Particle Physics (CERN), the Institute Laue Langevin (ILL), European Synchrotron Radiation Facility (ESRF), the European organisation for Astronomical Research in the Southern Hemisphere (ESO) and the European Space Agency (ESA). It also contributes money for the UK telescopes overseas on La Palma, Hawaii, Australia and in Chile, and the MERLIN/VLBI National Facility, which includes the Lovell Telescope at Jodrell Bank Observatory.

The Council is a partner in the UK space programme, coordinated by the British National Space Centre.

Source
Science and Technology Facilities Council

HOUSTON, July 8 — A majority of patients with type 2 neurofibromatosis had objective tumor responses to treatment with bevacizumab (Avastin), data from a small clinical trial showed.

• Explain to patients that a drug that blocks blood vessel growth in tumors shrank benign tumors related to a genetic condition that causes hearing loss.
• The study involved only 10 carefully selected patients.
• Point out that the effects of prolonged therapy are still not known.

Four of 10 patients had improved hearing, and two others had stable hearing during treatment, Scott Plotkin, MD, PhD, of Massachusetts General Hospital in Boston, and colleagues reported online in the New England Journal of Medicine.

Tumor responses remained durable in some patients during follow-up of 11 to 16 months.

“This kind of treatment response is unprecedented,” Dr. Plotkin said in a statement. “Our study is the first to provide evidence that a drug can shrink vestibular schwannomas . . . and the first to show that patients’ hearing can be improved.”

Bilateral vestibular schwannomas, or acoustic neuromas, are a hallmark feature of type 2 neurofibromatosis. Though benign, the tumors cause progressive hearing loss in most patients.

For patients with sporadic unilateral vestibular schwannomas, surgery and radiation therapy are effective at achieving tumor control, but frequently lead to hearing loss in the affected ear, the authors noted.

Treatment options are limited for patients who have a growing vestibular schwannoma ipsilateral to the only ear with hearing. Surgery and radiation therapy achieve tumor control less frequently, and the risk of hearing loss is increased.

However, unchecked tumor growth also can have severe consequences, which include progressive brain-stem compression.

VEGF and its receptor (VEGFR-1) are expressed in schwannomas, and increased expression correlates with an increased rate of tumor growth, the authors continued. Although schwannomas are not considered vascular tumors, the association between VEGF expression and tumor growth provided a rationale for evaluating bevacizumab in patients with type 2 neurofibromatosis.

The authors reported findings from a series of 10 patients with type 2 neurofibromatosis and evidence of progressive vestibular schwannomas. The patients were considered poor candidates for surgery or radiation therapy or had refused the therapies.

Immunohistochemical analysis revealed VEGF expression in 100% of the schwannomas. The tumors had a median pretreatment volumetric growth rate of 62%.

Six men and four women, whose median age was 25, received intravenous bevacizumab at a dose of 5 mg/kg every two weeks. Treatment ranged from three to 19 months, and six patients were followed for at least a year.

The anti-VEGF therapy led to tumor shrinkage in nine of 10 patients, and six had an imaging response, defined as a reduction in tumor volume of at least 20%. Four of the six patients had persistent responses during follow-up for 11 to 16 months.

Four of seven evaluable patients had a hearing response, defined as a significant increase in word-recognition score from baseline. Two other patients had stable disease, and only one had progressive hearing loss.

In one patient who did not have tumor shrinkage or hearing improvement, the treatment alleviated headaches and nausea caused by brainstem compression. The improvement allowed the patient to return to school.

“There has been a dogma that these tumors do not produce edema and are not angiogenic, concepts that now need to be re-evaluated,” said co-author Emmanuelle di Tomaso, PhD, also of Massachusetts General Hospital.

The work also suggests that VEGF has a role in nerve physiology, beyond angiogenesis.

Investigators documented 21 adverse events, all of which were grade 1 or 2 in severity. The most common events were elevated liver enzymes (seven events), proteinuria (three), and two episodes each of hypertension, delayed wound healing, hyperkalemia, and hyperbilirubinemia.

Two patients had vascular access ports that required removal. No patients had thromboembolic events, hemorrhage, gastrointestinal perforation, congestive heart failure, or reversible posterior leukoencephalopathy.

They pointed out, however, that “patients with benign tumors who benefit from anti-VEGF therapy present unique clinical challenges: they may have prolonged survival during which unanticipated delayed toxic effects could become manifest, and the implications of stopping therapy are unknown, with the potential for rebound tumor growth when monoclonal treatment is stopped.”

On the basis of the results, investigators have initiated a clinical trial of an investigational oral VEGF inhibitor in patients with type 2 neurofibromatosis.

The trial was supported by Harvard Medical School Center for Neurofibromatosis and Allied Disorders, Neurofibromatosis, New England, The Children’s Tumor Foundation, the Neurofibromatosis Research Program of the Department of Defense, the National Institutes of Health, and the Federal Share/National Cancer Institute Proton Beam Program. Dr. Plotkin disclosed relationships with Novartis and Pfizer. Co-author Gregory Sorensen disclosed relationships with AstraZeneca, Exelixis, Schering-Plough, Genentech, Novartis, Takeda-Millennium, Siemens Medical Solutions, Bayer Healthcare, and Mitsubishi Pharma. Co-author Rakesh Jain disclosed relationships with AstraZeneca, Dyax, Enlight, Millennium, Roche Pharmaceuticals, Pfizer, and SynDevRx.

Primary source: New England Journal of Medicine

Source reference:
Plotkin SR, et al “Hearing improvement after bevacizumab in patients with neurofibromatosis type 2″ N Engl J Med 2009; 361: 358-67.

A new prostate cancer “homing device” could improve detection and allow for the first targeted treatment of the disease.

A team of Purdue University researchers has synthesized a molecule that finds and penetrates prostate cancer cells and has created imaging agents and therapeutic drugs that can link to the molecule and be carried with it as cargo.

A radioimaging application used for body scans is expected to enter clinical trials this fall, and an optical imaging application used to measure prostate cancer cells in blood samples is already in clinical trials.

Philip Low, the Ralph C. Corley Distinguished Professor of Biochemistry who led the team, said a targeted treatment could be much more effective in treating cancer and would greatly reduce the harmful side effects associated with current treatments.

“Currently none of the drugs available to treat prostate cancer are targeted, which means they go everywhere in the body as opposed to only the tumor, and so are quite toxic for the patient,” said Low, who is a member of the Purdue Cancer Center. “By being able to target only the cancer cells, we could eliminate toxic side effects of treatments. In addition, the ability to target only the cancer cells can greatly improve imaging of the cancer to diagnose the disease, determine if it has spread or is responding to treatment.”

Prostate cancer is the most common cancer, other than skin cancers, and is the second leading cause of cancer death in American men, according to the American Cancer Society. It is estimated that about 192,280 new cases will be diagnosed and 27,360 men will die of prostate cancer in the United States this year.

The molecule Low’s team created attaches to prostate-specific membrane antigen, or PSMA, a protein that is found on the membrane of more than 90 percent of all prostate cancers. It also is found on the blood vessels of most solid tumors and could provide a way to cut off the tumor blood supply, Low said.

“A lot of new drugs are being designed to destroy the vasculature of solid tumors, and, if they could be linked to this new targeting molecule, we could have a two-pronged attack for prostate cancer,” he said. “We could not only kill the prostate cancer cells directly, we could also destroy the vasculature that feeds the tumors.”

There also is potential for the targeting molecule to be used to attack the vasculature of solid tumors of other types of cancers, Low said.

Two papers detailing the work of the Purdue team were published in the June 1 issue of Molecular Pharmaceutics. Endocyte Inc. funded the work.

The team’s animal study data shows an ability to eliminate human prostate cancer cells in mice with no evidence of collateral toxicity in normal tissue.

Sumith Kularatne, a graduate student in Purdue’s chemistry department and first author of both papers, compared the targeting molecule to a homing device.

“The molecule acts like a homing device for prostate cancer,” he said. “PSMA, which is found only on prostate cancer cells and tumor blood vessels, acts as the homing signal that the molecule targets. The molecule and its cargo go only to cancerous tissue, leaving healthy tissue unharmed.”

Once the molecule reaches the PSMA protein, it binds to it. The molecule is designed with a specific shape that fits with the protein like a key to a lock, Kularatne said. The molecule and its cargo are then carried inside the cell with the protein as it goes through its normal cycle.

In 1995 Low developed a similar method to infiltrate cancer cells by attaching treatments to the vitamin folate, which many cancers rapidly consume. This method provided a “Trojan Horse” entry of large treatment molecules that otherwise would not be able to enter cancer cells.

Low was inspired to find a similar way to target prostate cancer, which does not have the same appetite for folate, he said.

A clinical trial of the radioimaging application is expected to begin at the Indiana University Medical Center in the fall through a collaboration between the Purdue Cancer Center and the Indiana University Cancer Center with additional support from Endocyte Inc.

A radioimaging agent linked to the targeting molecule will be injected into prostate cancer patients and pictures will be taken using a special camera that detects radioactivity. The pictures show where the cancer is present to help doctors determine if it has metastasized, or spread, to any other areas of the body. It also will help doctors decide on the best course of treatment, Low said.

There is currently only one radioimaging agent for prostate cancer approved by the Food and Drug Administration .

“The current imaging capabilities available for prostate cancer are very poor,” Low said. “The existing imaging agent is limited because of its large size, which is difficult to get into a solid tumor. Also it seeks out a target located inside the cancer cell and is only able to mark injured cells that are falling apart as opposed to actively growing cancer cells.”

The targeting molecule and radioimaging agent combination designed by Low’s group is more than 150 times smaller than the existing agent and has much easier penetration through a solid tumor to reach all of the cells inside, he said. It also has the advantage of targeting an area of PSMA exposed on the outside of cancer cells.

Already in clinical trials is an optical imaging application that involves attaching a fluorescent dye to the targeting molecule and mixing it with a patient’s blood sample. Circulating prostate cancer cells in the sample fluoresce and are easily measured to help in diagnosing patients with prostate cancer. Researchers also are investigating whether this could be used to evaluate a patient’s response to therapy, Low said.

Low’s research group modeled the targeting molecule after a naturally occurring molecule that strongly binds to PSMA, called DUPA. Several alterations were necessary to create a molecule that fit the needs of a homing device and delivery vehicle, Kularatne said. The team created an area on the molecule that would link to various imaging or therapeutic agents to bring them along as cargo and created a spacer that would stretch the molecule so that its cargo would not keep it from properly fitting into the binding site. The spacer also was designed to improve binding of the targeting molecule to PSMA.

In addition to Low and Kularatne, co-authors of the papers include Endocyte researchers Kevin Wang and Hari-Krishna R. Santhapuram, graduate student in medicinal chemistry Zhigang Zhou, graduate student in chemistry Jun Yang, and professor of medicinal chemistry and molecular pharmacology Carol B. Post.

Low is the chief science officer for Endocyte, a Purdue Research Park-based company that develops receptor-targeted therapeutics for the treatment of cancer and autoimmune diseases. Endocyte holds the license to many of Low’s drug-targeting technologies.

Written by Elizabeth K. Gardner

Source
Purdue University