Louna Karam
Lebanese University, Lebanon
Title: The anti-tumor activities of the synthetic retinoid ST1926 against human herpes virus 8- associated primary effusion lymphoma
Biography
Biography: Louna Karam
Abstract
Primary effusion lymphoma (PEL) is a rare AIDS-associated B-cell neoplasm, caused by Human Herpes 8 virus (HHV8) infection. PEL has unique clinical manifestations, as it arises as malignant effusions in body cavities such as the pericardial, peritoneal cavities. PEL cells don't present conventional genetic cancer mutations; essentially its oncogenesis is attributed to HHV-8 latent genes, LANA-1, LANA-2, v-cyclin and v-FLIP, known to hold tumorigenic abilities. PEL is life threatening to immunocompromised and elderly people since it is known to relapse after standard chemotherapy treatments. Thus there is a need of new effective, targeted drugs. Among promising recent drugs, ST1926, a novel orally available, synthetic retinoid is promising antitumor agent having no-cross resistance with other chemotherapeutics. It was shown to exhibit a targeted apoptotic and genotoxic effect on a large panel of human solid and leukemic malignancies both in vitro and in vivo. The aim of this study is to elucidate the anti-tumor activities and underlying molecular mechanism, of ST1926 on PEL in vivo/ex-vivo/in vitro preclinical models. Pharmacologically achievable concentrations of ST1926 display potent anti-proliferative effect on PEL cell lines and their corresponding ascites. Also, ST1926 was shown to cause accumulation in preG1-population in cell cycle, as well as it induced apoptosis, DNA damage, PARP cleavage and P53 upregulation in PEL cells and ascites. In addition, ST1926 downregulated all tested viral latent transcripts in ex vivo ascites cells. The promising anti-cancer and anti-viral effects of ST1926 drugs could provide a novel basis for clinical application in PEL. Further, in vivo survival study on PEL-like NOD/SCID mice will be explored.