Cancer: shock breakthrough

The results were so startling that researchers decided to release details of the two cases before the drug trial – in which the patients took part – was complete. Doctors said their progress had exceeded all expectations. The men were treated at the Mayo Clinic in Minnesota in the US, one of the top medical centres in the world.

Dr Eugene Kwon, the urologist who was in charge of their treatment, compared the results to the first pilot breaking the sound barrier.

“This is one of the Holy Grails of prostate cancer research. We have been looking for this for years,” he said.

Prostate cancer is the most common cancer in men – 34,000 new cases and more than 10,000 deaths are reported each year in Britain, where rates of its occurrence have tripled in the past 30 years, mainly due to improved detection. The US has the highest incidence of the disease.

Rodger Nelson and Fructuoso Solano-Revuelta were diagnosed with advanced prostate cancer and sought treatment at the Mayo Clinic.

They were told the disease had spread beyond the prostate. Mr Nelson’s cancer was encroaching on the abdomen and Mr Solano-Revuelta’s tumour was the size of a golf ball. Patients in such condition are told they may have only months to live, and are normally only offered palliative care. But after one infusion of the drug ipilimumab, a monoclonal antibody that stimulates the immune system, given with conventional hormone therapy, their tumours shrank enough to be surgically removed. Both men have since made a full recovery and returned to their businesses.

The pair were part of a trial involving 108 patients, half of whom received the experimental drug. The trial is ongoing but the improvement of the two patients was so dramatic and unexpected that they were removed from the study so they could undergo curative surgery.

Dr Kwon said yesterday: “Halfway through the trial we began seeing remarkable responses. Some patients had dramatic shrinkage of their tumours so practically all traces had disappeared. We had thought we might get some incremental delay in the progression of the cancer. It had not dawned on us that we might go from an inoperable tumour to an operable one. That just doesn’t happen.”

The surgery would not have gone ahead if Carol Nelson, Mr Nelson’s wife and a former nurse, had not challenged the surgeons to attempt it.

“The idea of surgery on an ‘inoperable’ tumour had not dawned on us. It is often disappointing and not advisable. But she is a tough lady – and having been a nurse she knew how to control the doctors. We said we didn’t think surgery would work, but we would try,” Dr Kwon said.

The outcome was better than any of them could have anticipated. From having an enlarged prostate gland riddled with cancer which had spread, Mr Nelson was found to have a shrunk prostate gland with tiny pockets of cancer that were “very hard to find”.

Michael Blute, the surgeon who operated on Mr Nelson, said at one point doctors feared they might have the wrong patient: “I was cutting away scar tissue trying to find cancer cells. The pathologist was checking samples as we proceeded and sent word back asking if we had the right patient. He had a hard time finding any cancer. I have never seen anything like this before. The pathologists were floored.”

The procedure was repeated, with the same result, on Mr Solano-Revuelta. A third “inoperable” patient underwent surgery last week.

Dr Kwon said: “These were patients for whom there was no hope. The course of their disease has been altered in a dramatic fashion. We have a major finding which we never expected to stumble across but we have to complete our studies.”

He said the findings had to be confirmed in further studies and the results published in a peer-reviewed journal. A larger trial is due to begin in the autumn. The cases are described in the Mayo Clinic’s research publication, Discovery’s Edge.

Professor Malcolm Mason, a Cancer Research UK prostate cancer specialist, said: “These case reports are extremely interesting and encouraging. Ipilimumab might potentially be a strong stimulator of the immune system, and it seems logical that it might also be effective in prostate cancer.

“But caution is needed, as earlier trials with this drug in other types of cancer were less successful than reported here, and its true value can only become clear through large-scale, randomised clinical trials, two of which are already under way. The other cautionary note is that both men received hormone therapy, which in some instances causes dramatic reductions in tumour size by itself.”

Ipilimumab: How it works

*Ipilimumab is one of a class of drugs called monoclonal antibodies, which stimulate the body’s own immune system to fight disease. The experimental treatment is being developed by Bristol-Myers Squibb and Medarex, a US biotech company. The drug is being trialled on malignant melanoma, the most serious form of skin cancer, Hodgkin’s disease, lung cancer and prostate cancer. Studies are most advanced in melanoma, where it has been shown to prolong survival in patients with advanced forms of the disease. In the Mayo Clinic study of prostate cancer, researchers say that standard hormone treatment ignited the immune response, and adding ipilimumab was like “pouring gasoline on the pilot light”.

UCF researcher’s nanoparticles could someday lead to end of chemotherapy

Nanoparticles specially engineered by University of Central Florida Assistant Professor J. Manuel Perez and his colleagues could someday target and destroy tumors, sparing patients from toxic, whole-body chemotherapies.

Perez and his team used a drug called Taxol for their cell culture studies, recently published in the journal Small, because it is one of the most widely used chemotherapeutic drugs. Taxol normally causes many negative side effects because it travels throughout the body and damages healthy tissue as well as cancer cells.

The Taxol-carrying nanoparticles engineered in Perez’s laboratory are modified so they carry the drug only to the cancer cells, allowing targeted cancer treatment without harming healthy cells. This is achieved by attaching a vitamin (folic acid) derivative that cancer cells like to consume in high amounts.

Because the nanoparticles also carry a fluorescent dye and an iron oxide magnetic core, their locations within the cells and the body can be seen by optical imaging and magnetic resonance imaging (MRI). That allows a physician to see how the tumor is responding to the treatment.

The nanoparticles also can be engineered without the drug and used as imaging (contrast) agents for cancer. If there is no cancer, the biodegradable nanoparticles will not bind to the tissue and will be eliminated by the liver. The iron oxide core will be utilized as regular iron in the body.

“What’s unique about our work is that the nanoparticle has a dual role, as a diagnostic and therapeutic agent in a biodegradable and biocompatible vehicle,” Perez said.

Perez has spent the past five years looking at ways nanotechnology can be used to help diagnose, image and treat cancer and infectious diseases. It’s part of the quickly evolving world of nanomedicine.

The process works like this. Cancer cells in the tumor connect with the engineered nanoparticles via cell receptors that can be regarded as “doors” or “docking stations.” The nanoparticles enter the cell and release their cargo of iron oxide, fluorescent dye and drugs, allowing dual imaging and treatment.

“Although the results from the cell cultures are preliminary, they are very encouraging,” Perez said.

A new chemistry called “click chemistry” was utilized to attach the targeting molecule (folic acid) to the nanoparticles. This chemistry allows for the easy and specific attachment of molecules to nanoparticles without unwanted side products. It also allows for the easy attachment of other molecules to nanoparticles to specifically seek out particular tumors and other malignancies.

Perez’s study builds on his prior research published in the prestigious journal Angewandte Chemie Int. Ed. His work has been partially funded by a National Institutes of Health grant and a Nanoscience Technology Center start-up fund.

“Our work is an important beginning, because it demonstrates an avenue for using nanotechnology not only to diagnose but also to treat cancer, potentially at an early stage,” Perez said.

Perez, a Puerto Rico native, joined UCF in 2005. He works at UCF’s NanoScience Technology Center and Chemistry Department and in the Burnett School of Biomedical Sciences in the College of Medicine. He has a Ph.D. from Boston University in Biochemistry and completed postdoctoral training at Massachusetts General Hospital, Harvard Medical School’s teaching and research hospital.

Perez has broad experience in the academic, research and corporate worlds, having worked at Harvard Medical School, conducted research at Boston University and worked for the Millipore Corporation in Bedford, Mass. Since he joined UCF, he has written numerous articles in prestigious journals such as Nature Materials, Nanoletters, Small, PLOS One and Angewandte Chemie Int Ed.

UCF Stands For Opportunity –The University of Central Florida is a metropolitan research university that ranks as the 5th largest in the nation with more than 50,000 students. UCF’s first classes were offered in 1968. The university offers impressive academic and research environments that power the region’s economic development. UCF’s culture of opportunity is driven by our diversity, Orlando environment, history of entrepreneurship and our youth, relevance and energy. For more information visit http://news.ucf.edu

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Prototype breast cancer imaging system may improve patient care

A prototype breast imaging system combining positron emission tomography (PET) and magnetic resonance imaging (MRI) technologies could greatly improve breast cancer imaging capabilities, according to researchers at SNM’s 56th Annual Meeting.

Although the system has not yet been tested on humans, initial results from the prototype indicate the system produces a fusion of detailed PET and MRI images that should allow a more accurate classification of lesions in the breast.

“PET and MRI systems are both powerful, noninvasive tools for detecting breast cancer and evaluating treatment, but each of them also has weaknesses,” said Bosky Ravindranath, research assistant working with Dr. David Schlyer at Brookhaven National Laboratory, Upton, N.Y., and lead author of a study on preliminary testing of the prototype. “We believe that combining PET and MRI in a single system will eventually yield highly sensitive and specific breast cancer examinations while at the same time compensating for the shortcomings that exist when using only PET or only MRI.”

Conceptual drawings of the simultaneous PET/MRI breast imaging system being developed at Brookhaven Lab showing the how the PET insert (green) fits inside the MRI scanner and how it will be used with breast cancer patients.

When completed, the dedicated breast PET-MRI system will consist of a modular 3D tomographic PET scanner that is inserted inside a dedicated breast MRI coil produced by Aurora Technologies, Inc allowing both PET and MRI images to be taken simultaneously. The modularity of the PET system would allow for the scanner diameter to be adjusted according to patient breast size. Researchers expect the combined modality scanner will provide anatomical information from the MRI to enhance the resolution provided by PET. At the same time, the predictive power of PET in identifying the type of tumor should be able to overcome MRI technology’s traditionally high false-positive rates.

Based on the positive preliminary results, researchers expect to begin testing the system shortly with breast cancer patients.

Close up of the PET part of the breast imaging system, showing the individual detector units. This device was developed at Brookhaven Lab in a collaboration of the Medical Department, Physics Department, Instrumentation Division, and Stony Brook University.

Scientific Paper 249: B. Ravindranath, S. Junnarker, S.H. Maramraju; S. Southekal, M. Purschke, S. Stoll, D. Tomasi, P. Vaska, C. Woody, D. Schyler, Department of Biomedical Engineering, Stony Brook University, Stony Brook, N.Y.; and Brookhaven National Laboratory, Upton, N.Y. “Initial results from the BNL dedicated simultaneous PET-MRI breast imaging system prototype,” SNM’s 56th Annual Meeting, June 13-17, 2009.

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