Anti-IFNG monoclonal antibody, clone 5T.C4 [Brilliant Violet 570]

Despite the enormous development of medical technologies in recent decades, pituitary adenoma (PA) remains among the most refractory cancers in the world. Elucidating the molecular mechanisms underlying the pathology of PA is essential to identify new treatments for PA. In the present study, we found that IFNG-AS1 expression was significantly higher in PA tissues than in nontumor tissues via qRT-PCR and RNA fluorescence in situ hybridization (FISH). shRNA-mediated IFNG-AS1 knockdown in HP75 cells significantly inhibited tumor progression, and IFNG-AS1 overexpression remarkably promoted tumor progression. Epithelial splicing regulatory protein 2 (ESRP2) was demonstrated to be a target protein of IFNG-AS1 in PA; knocking down ESRP2 reversed the tumor-inhibitory effects of IFNG-AS1 knockdown, and overexpressing ESRP2 abolished the tumor-promoting effects of IFNG-AS1 overexpression in HP75 cells. In conclusion, our findings suggested that IFNG-AS1 may function as an oncogene in PA by interacting with ESRP2.

Hepatocellular carcinoma (HCC) is a heterogeneous disease. Mouse models are commonly used as preclinical models to study hepatocarcinogenesis, but how well these models recapitulate molecular subtypes of human HCC is unclear. Here, integration of genomic signatures from molecularly and clinically defined human HCC (n = 11) and mouse models of HCC (n = 9) identified the mouse models that best resembled subtypes of human HCC and determined the clinical relevance of each model. Mst1/2 knockout (KO), Sav1 KO, and SV40 T antigen mouse models effectively recapitulated subtypes of human HCC with a poor prognosis, whereas the Myc transgenic model best resembled human HCCs with a more favorable prognosis. The Myc model was also associated with activation of beta-catenin. E2f1, E2f1/Myc, E2f1/Tgfa, and diethylnitrosamine (DEN)-induced models were heterogeneous and were unequally split into poor and favor-able prognoses. Mst1/2 KO and Sav1 KO models best resemble human HCC with hepatic stem cell characteristics. Applying a genomic predictor for immunotherapy, the six-gene IFNg score, the Mst1/2 KO, Sav1 KO, SV40, and DEN models were predicted to be the least responsive to immunotherapy. Further analysis showed that elevated expression of immuneinhibitory genes (Cd276 and Nectin2/Pvrl2) in Mst1/2 KO, Sav1 KO, and SV40 models and decreased expression of immune stimulatory gene (Cd86) in the DEN model might be accountable for the lack of predictive response to immunotherapy. Implication: The current genomic approach identified the most relevant mouse models to human liver cancer and suggests immunotherapeutic potential for the treatment of specific subtypes. (C) 2018 AACR.