How do certain multiple myeloma treatment drugs cause complications? How does the immune system become dysfunctional due to cancer? How safe is a vaccine that could prevent development of precancerous colon polyps? Those are among the many questions that will be answered by researchers from the University of Pittsburgh Cancer Institute (UPCI) and the University of Pittsburgh School of Medicine during the American Association for Cancer Research 102nd Annual Meeting 2011, April 2 to 6, in Orlando, Fla.
UPCI and Pitt researchers will present more than 80 posters, talks and tutorials, as well as lead educational sessions and chair panel discussions during the event.
Highlights include: ORAL PRESENTATIONS:
Mechanisms of Complications of Multiple Myeloma Treatments
Suzanne Lentzsch, M.D., Ph.D., assistant professor of medicine and clinical director of the multiple myeloma program at UPCI, will discuss her research that shows how immunomodulatory derivatives of thalidomide (IMiDs), such as lenalidomide and pomalidomide, used in multiple myeloma treatment also affect blood cell production pathways by decreasing production of a key protein needed for blood cell specialization.
"That leads to treatment complications including a reduction in the numbers of neutrophils, a kind of white blood cell, and an increase in a protein that promotes platelet clumping that in turn increases the risk for blood clots," Dr. Lentzsch explained.
Inflammatory Mediator Drives Suppressor Cells That Cause Immune System Dysfunction in Cancer
Natasa Obermajer, Ph.D., a postdoctoral fellow, will present a project conducted in the lab of senior investigator Pawel Kalinski, M.D., Ph.D., professor of surgery and UPCI researcher, that shows a single cancer-associated inflammatory mediator called prostaglandin E2 (PGE2) drives the differentiation and stability of myeloid-derived suppressor cells that play a key role in causing immune system dysfunction and a microenvironment that allows cancer cells to thrive.
"Our findings suggest that a positive feedback loop exists between PGE2 and COX-2, which regulates PGE2 production," Dr. Kalinski said. "When we disrupted this feedback loop in suppressor cells taken from cancer patients by blocking COX-2 or PGE2 signaling receptors, we stopped the cells' ability to suppress cancer-killing immune cells. This might be a new avenue to explore for future cancer treatments."
Cancer Vaccines Targeting Pre-Malignant Lesions
Olivera Finn, Ph.D., professor and chair, Department of Immunology, will present her work in developing vaccines that target abnormal peptides, or small pieces of protein, that are produced during the development of certain cancers. Tumor formation might be prevented with a vaccine that generates an immune response against the cells that carry these worrisome peptides.
"Vaccines that are administered as a possible treatment after cancer has already developed have not been very effective," she noted. "But if we can help the immune system find these dangerous cells in people who are at high risk for cancer but are still healthy, we might have an intervention that could prevent many cases of disease."
With colleagues including clinical collaborator Robert E. Schoen, M.D., professor of medicine, Dr. Finn also is presenting a poster (EMBARGOED until 8 a.m., Wednesday, April 6) of preliminary findings of a colon cancer prevention vaccine that is being tested for safety at UPMC. None of the vaccine recipients who have been evaluated had significant side effects, and half of them generated an immune response to MUC1, the vaccine target and a protein that becomes aberrant during the progression of advanced colon polyps into cancer. These early findings encourage further testing in a randomized trial to assess whether the vaccine can prevent recurrence of adenomatous polyps. Abstract 5510POSTER PRESENTATIONS:
Novel Drug Protects Esophagus After Radiation Exposure
Mice that swallowed the experimental drug JP4-039 before they were exposed to upper body radiation were more likely to survive than untreated animals. Of the treated animals, 75 percent survived for 30 days after exposure compared to 30 percent of the untreated group. The findings could lead to drugs that prevent esophagitis, a typical side effect of radiation treatment for lung cancer. Abstract 2502
Seizure Drug Offers Protection from Radiation Exposure
In cell and mouse experiments, carbamazepine, a drug typically prescribed to treat mood disorders, epilepsy and trigeminal neuralgia, mitigated the impact of radiation exposure by increasing autophagy, a process in which the cell components are degraded and discarded. Abstract 2495