Research Briefs: March 2016

Finding New Targets for Melanoma Care

Melanoma is the most aggressive type of skin cancer that is easy to treat when it’s caught early, and very difficult to treat once it has grown and spread in the body, via metastasis. In the past decade, however, researchers have made headway into therapies to treat metastatic melanoma, where in the past there have been few viable options. One of the two most successful approaches includes gene-targeting therapies and researchers at Jefferson are looking to ways of improving existing drugs in this area.

One gene that controls normal cell growth, called B-RAF, is mutated in about 50 percent of melanomas, causing the cell to spur uncontrolled growth and metastasis in these skin cells. Several drugs exist to block BRAF, but after a while, the cancer develops resistance to the medication, relying on other genes to spur growth. Andrew Aplin, a Professor of Cancer Biology at Thomas Jefferson University and researcher at the Sidney Kimmel Cancer Center has received a National Institutes of Health RO1 grant to help discover other genes that fuel melanoma growth after BRAF is rendered inactive by these drugs, thus opening new avenues for creating add-on gene-targeting therapies for melanoma.

Already, Dr. Aplin’s team has identified a number of candidate genes and is investigating just how these genes interact with the mutated version of BRAF that drives cancer growth.

Vitamin D Deficiency Associated with Cystic Fibrosis

Patients with cystic fibrosis struggle with lungs that become clogged with mucous. Researchers have found that these patients often have very low levels of vitamin D. Now, a new study from Jefferson researcher lead by Dr. William Sexauer, Clinical Professor in the Division of Pulmonary Medicine and the Director of Critical Care at Methodist Hospital-Jefferson Health tested whether  vitamin D deficiency might contribute to the lung disease characteristic of cystic fibrosis.

The researchers looked at nearly 600 cystic fibrosis patients whose vitamin D levels had been measured within two months of completing a common lung-health assessment. Patients who fared worse on a lung-function test called the forced expiratory volume had lower levels of vitamin D in their blood.

Whether cystic fibrosis patients would benefit from vitamin D supplementation is still an open question, says Dr. Sexauer, but this study suggests that it may be worth exploring in a clinical trial.

One Key to Fewer Kidney Transplants for Young Patients

Kidney transplants often don’t last the life time of the recipient, so young patients with renal failure will often require multiple transplants over their lifetime. With each transplant, a patient’s immune system can develop resistance to future transplants due to development of antibodies, a phenomenon known as sensitization. New research from senior author Adam Frank, Associate Professor in the Division of Transplant Surgery, and first author Pooja Singh, an Assistant Professor in the Division of Nephrology at Jefferson has put a known tool to a new use to help determine a patient’s risk for future sensitization.

A handful of immune markers, known as human leukocyte antigens or HLA, are typically tested in order to match a transplant patient with a donor. While a complete match is not required for kidney transplantation, Singh, Frank and colleagues showed that one less-commonly tested HLA marker plays an important role in determining high risk of developing sensitization and thus future kidney rejection. By looking for common characteristics between recipients who developed very high sensitization after kidney failure, the researchers found that the antigen called the DQ eplet was frequently mismatched. The work suggested that when the DQ eplet is mismatched between a kidney donor and recipient, the recipient is more likely to face hurdles in undergoing future kidney transplants.

“This requires a shift in thinking about transplantation for those patients who will require multiple transplants over the course of their lives,” says Dr.  Singh, who is the corresponding author of the study. “The best transplant for them may not be the one that is immediately available, but rather the one that has the best match, especially in the DQ locus.”

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