ABSTRACT
Combination therapies may increase the antitumor effects and reduce the adverse effects for the treatment of hepatocellular carcinoma. In this study, we determined the effects of 5-fluorouracil alone or in combination with wogonin in vitro and in vivo, and we investigated the possible mechanisms. The combination of these 2 drugs led to a decrease in survival and a significant synergistic inhibitory effect on high COX-2 expression in SMMC-7721 hepatocellular carcinoma (HCC) cells. Furthermore, the results show that this combination inhibits COX-2 expression and increases sensitivity to chemotherapeutic agents partly through regulating the PI3K/Akt signaling pathway. Moreover, the combination treatment caused a significant growth inhibition of human tumor xenografts in vivo. In conclusion, wogonin may increase the cytotoxicity of some antineoplastic agents and it can be used in combination with these agents as a novel therapeutic regimen for HCC treatment.
Subject(s)
Carcinoma, Hepatocellular/metabolism , Cyclooxygenase 2/metabolism , Cyclooxygenase Inhibitors/administration & dosage , Flavanones/administration & dosage , Fluorouracil/administration & dosage , Liver Neoplasms/metabolism , Signal Transduction , Animals , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Cell Line, Tumor , Cell Proliferation , Dinoprostone/metabolism , Drug Synergism , Female , Gene Expression Regulation, Neoplastic , Hep G2 Cells , Humans , Mice , Mice, Inbred BALB C , Mice, Nude , Neoplasm Transplantation , Phosphatidylinositol 3-Kinases/metabolism , Plant Extracts/pharmacology , Proto-Oncogene Proteins c-akt/metabolismABSTRACT
Therapeutic monoclonal antibodies have become an important class of modern medicines. The established technologies for therapeutic antibody discovery such as humanization of mouse antibodies, phage display of human antibody libraries and transgenic animals harboring human IgG genes have been practiced successfully so far, and many incremental improvements are being made constantly. These methodologies are responsible for currently marketed therapeutic antibodies and for the biopharma industry pipeline which are concentrated on only a few dozen targets. A key challenge for wider application of biotherapeutic approaches is the paucity of truly validated targets for biotherapeutic intervention. The efforts to expand the target space include taking the pathway approach to study the disease correlation. Since many new targets are multi-spanning and multimeric membrane proteins there is a need to develop more effective methods to generate antibodies against these difficult targets. The pharmaceutical properties of therapeutic antibodies are an active area for study concentrating on biophysical characteristics such as thermal stability and aggregation propensity. The immunogenicity of biotherapeutics in humans is a very complex issue and there are no truly predictive animal models to rely on. The in silico and T-cell response approaches identify the potential for immunogenicity; however, one needs contingency plans for emergence of anti-product antibody response for clinical trials.
ABSTRACT
OBJECTIVES: To understand the vaccination situation of left-behind children in rural areas, provide the evidence for developing vaccination strategies for left-behind children. METHODS: The counties with population over 1,000,000 were selected from Anhui and Sichuan provinces respectively to conduct survery to the children who were born between the year 2003 and 2006, and had registration on vaccination book(card). RESULTS: The proportion of left-behind and outflow children are 17.94% and 6.05% respectively. The information about the children's parents going out most came from village doctors. The proportion of the parents going out after children born was 51.60%, staying outside for more than 10 months was 78.50%. 67.97% parents came back home during the spring festival, 35.43% left-behind children went out with their parents. CONCLUSION: Although the number of outflow children was smaller than the left-behind children, it was easy to develop immunization gap. It is the difficult part of management on EPI to migrant children. The information aboat the children's parents going out mostly came from village doctors. It is important to mobilize the enthusiasm of doctors. It is especially essential that we should propagandize to the people with vaccination knowledge to the parents came back home during spring festival.
