This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. We are continuing our collaborative project with Dr. Laura Levy in examining lymphomas in SIV-infected and uninfected rhesus macaques. To date, we have identified 50 cases of simian AIDS-related lymphoma (sARL) and 108 control animals age-matched for species, gender and age at SIV inoculation. We then assembled longitudinally collected laboratory and clinical data on all animals relating to survival time, absolute and relative B-cell and T-cell counts, rate of B-cell and T-cell change over the disease course, clinical evidence of lymphoid hyperplasia, and peripheral blood antigenemia. The data were than analyzed statistically in a case-control manner. The statistical analysis was recently completed, and proved to be exhaustive. At least 500 pages of output resulted, which we expect to review and interpret over the next few months. We are seeking statistically significant correlations between laboratory or clinical findings and early disease onset, such that such findings might have predictive value for the later development of lymphoma. Over the past funding year, we have made substantial progress in dissecting the complex network of regulation that controls the growth of ARL-derived cells. We focused on the independent and interacting influences of two cytokines that are expressed in simian ARL (sARL), i.e., IL-6 and TGF-beta1. Specifically, our studies have shown the sARL-derived cell line, LCL8664, was sensitive to growth inhibition by TGF-beta1, that IL-6 appears to increase proliferation and cell viability through multiple mechanisms, including partially blocking the cell cycle arrest and apoptosis induced by TGF-beta1.
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