Research, supported by Voelcker Fund, explains why some human lymphomas can be deadly

SAN ANTONIO (April 9, 2010) — Annually 30,000 Americans are diagnosed with diffuse large B-cell lymphoma, a type of cancer of the lymphatic system. Approximately half will die of this disease despite the latest, state-of-the-art treatment.

A recent research finding from The University of Texas Health Science Center at San Antonio points to a potential new way to cure this type of lymphoma — by dampening the activity of a gene that makes the cancers more aggressive. Generous funding from The Max and Minnie Tomerlin Voelcker Fund supported this research.

“Importantly, the patients with the most ominous outcomes also have the highest levels of this gene, called microRNA-155, in their tumor cells,” said Ricardo Aguiar, M.D., Ph.D., assistant professor of hematology and medical oncology in the Health Science Center School of Medicine. “Thus, understanding the mechanism by which microRNA-155 contributes to the tumor’s aggressiveness is essential to improving the cure rate in this type of lymphoma.”

He called the dependence on microRNA-155 “a chink in the armor of this cancer cell.”

The finding also is important because microRNA-155 is abnormally expressed in several other aggressive tumor types, and thus the findings in lymphoma are likely to benefit a broad spectrum of cancer patients, Dr. Aguiar said.

Series of events = bad tumor

The research team studied lymphoma cells that were modified to express too much or too little of microRNA-155. An excess of this gene in lymphomas strongly inhibited a particular protein, which in turn blocked the activity of tumor-suppressing signals of the transforming growth factor beta (TGF-β) signaling pathway. The TGF-β pathway regulates development, cell growth, cell death and many other key functions in cells.

“The end result is that the lymphoma is more aggressive,” Dr. Aguiar said.

The researchers next studied diffuse large B-cell lymphoma in a mouse model of the disease and were able, through specialized bioluminescent scans, to precisely measure the effects of microRNA-155 in the tumor’s aggressiveness.

The last stage of the study was to document the same findings in lymphomas from human patients.

The research was published this year in Proceedings of the National Academy of Sciences. Authors, all from the Health Science Center, are Deepak Rai, Ph.D. (first author); Sang-Woo Kim, Ph.D.; Morgan R. McKeller, Ph.D.; Patricia L.M. Dahia, M.D., Ph.D.; and Dr. Aguiar. Dr. Aguiar also is a member of the Experimental and Developmental Therapeutics Program of the Cancer Therapy & Research Center at the UT Health Science Center San Antonio.

Treatment armamentarium

“Our study helped in determining why lymphomas that have excessive amounts of microRNA-155 are so aggressive and often fatal for the patients,” Dr. Aguiar said. “This knowledge will significantly enhance our chances to cure a larger fraction of lymphoma patients with the use of a sophisticated treatment armamentarium that targets the vulnerability of the cancer cell.”

NOTE: Dr. Aguiar is supported by a $750,000 Young Investigator Award from The Max and Minnie Tomerlin Voelcker Fund. The Voelcker Fund awarded Young Investigator or Scholar grants to six Health Science Center faculty in 2009. Max and Minnie Tomerlin Voelcker, who died in 1980 and 2000, respectively, ran a successful dairy farm in San Antonio for many years. The Voelckers loved children and San Antonio and were deeply interested in medical research. The Voelcker Fund has donated more than $8.75 million to The University of Texas Health Science Center at San Antonio for translation of research into treatments for cancer and other diseases.

The University of Texas Health Science Center at San Antonio, one of the country’s leading health sciences universities, ranks in the top 2 percent of all U.S. institutions receiving federal funding. Research and other sponsored program activity totaled a record $259 million in fiscal year 2009. The university’s schools of medicine, nursing, dentistry, health professions and graduate biomedical sciences have produced 27,000 graduates. The $753 million operating budget supports six campuses in San Antonio, Laredo, Harlingen and Edinburg. For more information on the many ways “We make lives better®,”

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