jueves, 30 de junio de 2011

Imaging Boot Camp for Cancer Researchers - NCI Cancer Bulletin for June 28, 2011 - National Cancer Institute

This is the seventh article in a series of stories related to new technology in cancer research. You can read more articles in the series here.

Imaging Boot Camp for Cancer Researchers

Students at NCI's Cancer Research Imaging Camp get a lesson in using contrast to improve the visibility of a tumor on an MRI scan. (Photo by Sharon Reynolds)

In a basement lab, a group of students gently place a tumor-bearing mouse into the bore of a small-animal MRI machine to test several methods for distinguishing cancer from surrounding fat cells. Upstairs, another group of scientists rotates through three optical imaging stations, observing the different ways that visible and infrared light can be harnessed to visualize cancer cells in a mouse. At the ultrasound table, a young researcher uses a receiver to deliver a burst of energy to a small tumor in vivo, lighting up a contrast agent designed to bind to and highlight tumor blood vessels.

NCI's annual Cancer Research Imaging Camp, sponsored by the Cancer Imaging Program (CIP) and held June 19–24 this year at Washington University in St. Louis, provides a one-of-a-kind immersive experience for junior scientists eager to incorporate modern imaging methods into their research. Trainees can't possibly gain a comprehensive understanding of imaging technology in 6 days, but that's not the goal of the program, explained Dr. Kenneth Krohn, professor of radiology, radiation oncology, and chemistry at the University of Washington in Seattle and an instructor at Imaging Camp since its inception.

"What we want them to take away is that there are lots of evolving technologies, and that the most important thing is for them to formulate their research questions first and then find the best technology to answer those questions." What researchers should avoid, said Dr. Krohn, is using an imaging method in their research simply because they are familiar with it, or because it has been the only thing available to them.

Although some Imaging Camp participants have experience with one or more of the methods taught during the week, many are learning these methods for the first time.

By the third day of this year's program, Dr. Ashley Snider, an assistant professor of medicine and lipid researcher at the Medical University of South Carolina and the Ralph H Johnson VA Medical Center, and novice imager, had already picked up some ideas. She is working on a collaborative project with two senior cancer researchers, looking at how colon cancer forms in patients with ulcerative colitis. Dr. Snider plans to test some of the techniques she learned at Imaging Camp to monitor the overproduction of blood vessels and track drug delivery in the colon.

"I had never done in vivo imaging before camp," she said. "We'd seen in cells and in animals that an inflammation-associated lipid…contributes to carcinogenesis, but we want to take that work to the next level and monitor the response of tumors to inhibitors we're developing with in vivo imaging. That's why I'm here."

Setting Up Camp

The idea for Imaging Camp sprang from NCI's Imaging Integration and Implementation (I2) group, which was set up in 2004 to encourage greater use of imaging in cancer research. Early on, the group recruited Dr. Bonnie Sloane, distinguished professor and chair of pharmacology at Wayne State University, as a liaison to the CIP to help cancer biologists gain a better understanding of imaging techniques. She identified a basic lack of training as the main barrier to greater use of imaging in cancer biology.

Two Imaging Camp students watch a demonstration of a fluorescent probe used to highlight a tumor for optical imaging. (Photo by Sharon Reynolds)

"If you're trained, it's easy to use a technology. But if you don't understand the modalities and the pluses and minuses of each, you don't know how they could help answer your research questions," she explained. Conceived in 2005 and launched in 2007, Imaging Camp draws junior researchers from diverse disciplines that intersect with cancer biology and treatment.

"It's amazing how imaging has infiltrated this field completely," commented Dr. Suresh Mohla, associate director of NCI's Division of Cancer Biology, who co-chaired the Imaging I2 group. "More and more people are using whole-animal imaging to monitor tumor progression, to understand the behavior of tumors and surrounding cells. It's opened up a whole new perspective on how cancer develops in vivo that wasn't available before, and this program is contributing to training the next generation of cancer researchers in these innovative techniques," he continued.

"We hope that the Imaging Camp students will become the experts of the future, and train their own students. Since we can't train hundreds each year, we're trying to sow the seeds," Dr. Mohla explained.

Labor of Love

For its first 2 years, the camp was hosted by Duke University before the mantle was passed to Washington University in St. Louis in 2009. Beginning next year, the camp will be held at Vanderbilt University. Each year, the all-volunteer faculty members come from these and a dozen other institutions around the country to teach, and many have been instructors since the program began.

The planning—including logistics, recruiting new instructors, and managing the animal models required for the program—takes a good part of the preceding year, explained Drs. Joseph Ackerman and Joel Garbow of Washington University, who have served as the program hosts for the past 3 years.

"But it's such a labor of love for these faculty," said Dr. Anne Menkens, program director of the CIP's Molecular Imaging Branch and NCI coordinator of Imaging Camp. "We don't have to spend any time cajoling people into participating. Training the next generation is what drives them."

The student-to-faculty ratio is kept almost one-to-one; having only 25 students attend each year allows for nearly constant interaction between the imaging experts and the trainees. The faculty often learns new facts about cancer biology from the students, recounted Dr. Cristian Badea, a physicist and associate professor of radiology at Duke who has served as an instructor since Imaging Camp's first year.

"Every camp is a new experience. People bring all kinds of expertise, and I learn new things every year from the participants," he said. "I think the future of imaging is multidisciplinary, and while we're here we can start to break down the barriers of communication between the disciplines."

Through these conversations, "the students learn to talk to the imagers, the lingo, what to ask about their research," Dr. Sloane elaborated. "This is critically important because a lot of [imaging technology] is so sophisticated, a lot of junior people who haven't been exposed to it can be intimidated."

Creating Collaborations and Professional Relationships

Imaging Camp emphasizes collaboration and cooperation. The process begins on the first night, when participants present their current research and solicit ideas from the audience—both faculty and fellow students. Sharing continues in the halls as students are encouraged to swap papers and suggestions, many of which have led to collaborative projects among the trainees, said Dr. Menkens. The collaboration and cooperation continues in formal question-and-answer sessions designed to make sure that every question reaches the most appropriate experts.

The faculty also helps point the new imaging researchers toward potential mentors, bringing the trainees into their own extensive networks. "We encourage them to use the expertise of the camp to help them find a laboratory to work with that has that technology they need," said Dr. Krohn.

Sometimes those mentors are Imaging Camp faculty. Dr. Sloane has hosted a former Imaging Camp student who wanted more optical imaging experience. Dr. Samuel Achilefu, a professor of radiology at Washington University, who has run the optical imaging program at Imaging Camp for the past 4 years, is proud that several former students from Imaging Camp have collaborated with his group.

Some of these collaborations have turned into major projects. Dr. Garbow is participating in the first year of research on a grant won by Dr. Cheryl Jorcyk, an associate professor at Boise State University who attended Imaging Camp in 2009. "By chance we sat down next to each other at dinner, and when we stood up we had a research plan," remembered Dr. Garbow.

Their research project, funded by the Susan G. Komen for the Cure foundation, combines Dr. Jorcyk's expertise in the biology of breast cancer metastasis with Dr. Garbow's experience in imaging small-animal models of cancer. "I think our project is a model for the way collaborations might develop through this kind of training program," concluded Dr. Garbow.

Sharon Reynolds
Cancer Research Imaging Camp StudentsEvery year, 25 students are selected for the Cancer Research Imaging Camp. They come from diverse backgrounds, including chemistry, molecular biology, pharmacology, and even comparative oncology. Read profiles of three students and their interest in imaging training below.

Dr. Monique Spillman

Dr. Monique Spillman
Assistant Professor of Gynecologic OncologyUniversity of Colorado, Denver
For her research on the effects of estrogen and progesterone on ovarian cancer, Dr. Spillman had previously developed a mouse xenograft model and used fluorescence to detect cancer cells within the abdomen, but that technique "lacks sensitivity for deep lymph node metastases," which is an area of translational research she and her colleagues hope to explore, she explained. Lymph-node staging for women with early-stage ovarian cancer, which is vital for determining appropriate treatment, currently requires extensive surgical sampling. An in vivo imaging probe that recognizes deep metastases "would be less invasive and more informative," and could also be used in her laboratory to better understand the biology driving the spread of ovarian cancer to lymph nodes.

Dr. Vijay Ramakrishnan
Dr. Vijay Ramakrishnan
Postdoctoral Researcher in HematologyMayo Clinic
Dr. Ramakrishnan has been testing novel drugs and drug combinations on human multiple myeloma cell lines and in cells taken from patients, examining the role of bone marrow stromal cells and endothelial cells in disease progression. "We know that the bone marrow stromal cells and endothelial cells interact, but we don't understand how that interaction affects disease progression and response to chemotherapy," Dr. Ramakrishnan explained. He hopes to develop an animal model to monitor these interactions noninvasively in vivo. But before he attended Imaging Camp, Dr. Ramakrishnan had no experience with imaging. "[My colleagues and I] think both in vivo and live-cell imaging are going to be very informative as to how these cell-cell interactions are altered after treatment with particular chemotherapy agents," he said.

Dr. Jackie Wypij
Dr. Jackie Wypij
Assistant Professor of Veterinary Clinical MedicineUniversity of Illinois, Urbana-Champaign

As a member of the Comparative Oncology Trials Consortium, Dr. Wypij not only works on clinical trials of novel therapies for pets with cancer, she also looks for ways to translate her knowledge to human cancers. "There's a big black box between mouse and human research, and maybe our patients can fill this in. The genetics in some canine and feline cancers are quite close to some human cancers," she explained. "People are interested in having their pets participate in trials. They want to do it for their pets, but they also feel good about giving something back, that they might be helping people in the future as well." Her group does a lot of clinical imaging for dogs and cats, but "we don't yet incorporate the advanced research imaging methods into our research and trials, and that's what I'd like to do, particularly to look for biomarkers we can use for testing new treatments," she elaborated.

NCI Cancer Bulletin for June 28, 2011 - National Cancer Institute

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