ABSTRACT
Translational science is defined as the field of investigation focused on understanding the scientific and operational principles underlying each step of the translational process. Further development of the field is advanced by describing the key desirable characteristics of individuals who seek to uncover these principles to increase the efficiency and efficacy of translation. The members of Translation Together, a newly launched international collaborative effort to advance translational innovation, present here a consensus representation of the fundamental characteristics of a translational scientist. We invite all stakeholders to contribute in the ongoing efforts to develop the field and educate the next generation of translational scientists.
Subject(s)
COVID-19 , Civil Defense , Communicable Disease Control , Translational Research, Biomedical , COVID-19/epidemiology , COVID-19/prevention & control , Civil Defense/organization & administration , Civil Defense/trends , Communicable Disease Control/methods , Communicable Disease Control/organization & administration , Communicable Disease Control/trends , Communication Barriers , Drug Development , Forecasting , Global Health/standards , Global Health/trends , Humans , International Cooperation , Public Health , SARS-CoV-2 , Translational Research, Biomedical/methods , Translational Research, Biomedical/standards , Translational Research, Biomedical/trendsABSTRACT
To determine the effect on gene expression of trace levels of reactive oxygen species from mitochondria, we used the mRNA differential display technique to compare gene expression in two cell lines: M15, which overexpresses mitochondrial phospholipid hydroperoxide glutathione peroxidase (mtPHGPx), in rat basophilic leukemia RBL-2H3 cells, and a control cell line, S1. We isolated 27 differentially expressed genes, including 10 previously unreported sequences. These genes included cytoskeletal proteins (beta-tubulin, nonmuscle myosin alkali light chain, and vimentin), growth or proliferation regulators [growth differentiation factor 1 (Gdf-1), Rap1a, and inhibitor of growth 3 (Ing3)], and others. Although the expression of most of the isolated genes did not respond to ROS (hydrogen peroxide) or antioxidant (pyrolidine dithiocarbamate) treatment, the expression of Gdf-1 was downregulated by hydrogen peroxide treatment. Thus, low levels of ROS produced in mitochondria during normal cellular metabolism can modulate gene expression.
Subject(s)
Cytoskeletal Proteins/genetics , Gene Expression/drug effects , Glutathione Peroxidase/metabolism , Hydrogen Peroxide/pharmacology , Intercellular Signaling Peptides and Proteins/genetics , Mitochondria/enzymology , Nerve Tissue Proteins/genetics , Animals , Antioxidants/pharmacology , Down-Regulation , Gene Expression Profiling , Growth Differentiation Factor 1 , Phospholipid Hydroperoxide Glutathione Peroxidase , RNA, Messenger/genetics , RNA, Messenger/metabolism , Rats , Reactive Oxygen Species , Thiocarbamates/pharmacology , Tumor Cells, Cultured , Up-RegulationABSTRACT
BACKGROUND: Miriplatin (formerly SM-11355), a novel lipophilic platinum complex developed to treat hepatocellular carcinoma, is administered into the hepatic artery using an oily lymphographic agent (Lipiodol Ultra-Fluide) as a carrier. We clarified the usefulness of miriplatin as an agent for transarterial chemoembolization. METHODS: Platinum compounds released from miriplatin into serum, medium and Earle's balanced salt solution were examined. Then, miriplatin and cisplatin were administered to rats bearing hepatoma AH109A tumors in livers. Platinum concentrations in tissues and DNA were assessed. RESULTS: Miriplatin showed a more sustained release than cisplatin. Dichloro[(1R, 2R)-1, 2-cyclohexane diamine-N, N']platinum, the most abundant platinum compound released from miriplatin, was as effective as cisplatin in inhibiting the growth of cells. Miriplatin was selectively disposed of in tumors, maintained in tumors longer than cisplatin and caused apparent tumor regression inducing platinum-DNA adducts to form and massive apoptosis. CONCLUSION: Miriplatin appears to be a suitable chemotherapeutic agent for transarterial chemoembolization.