RESUMEN
For children suffering from primary nephrotic syndrome(PNS), podocyte is a crucial part of glomerular filtration barrier, whose injury usually causes proteinuria.The structural and functional integrity of podocyte cytoskeleton is the prerequisite of its normal physiological function.Recent studies demonstrated that under a certain pathological condition, B7-1, expressed in podocyte, can inhibit the activation of β1 integrin by competitively binding to the target site on the β1 integration, which may change the morphology and function of podocyte, consequently induced proteinuria.Other studies also have showed that abatacept, which selectively inhibit the cross-talk between B7-1 and β1-integrin,can reduce proteinuria in patients with B7-1-positive glomerular disease.These studies suggested that B7-1 may be a potential diagnostic biomarker and therapeutic target in proteinuria in PNS.This review summarizes the role of B7-1 expressed in podocyte in the pathogenesis of proteinuria and the possibility of clinical application in the future.
RESUMEN
BACKGROUND/AIMS: Immunogene therapy is extensively studied for a therapeutic modality of various cancers. This study was conducted to investigate the efficacy of immunogene therapy using the T-cell costimulatory molecule and human B7-1 (CD80, hB7-1) in an in vivo human hepatocellular carcinoma (HCC) model. METHODS: The stable HCC cell line expressing hB7-1 gene was established using retroviral vector (Huh-7/hB7-1). Of fourteen BALB/c nude mice, 7 were subcutaneously injected with 2 X 10(6) Huh-7/hB7-1 cells, while the other 7 were injected with 2 X 10(6) Huh-7/mock cells as a control group. After the injection, the mice were observed weekly for three months for subcutaneous tumor formation. Assay for natural killer (NK) cell cytotoxicity and serum IFN-gamma was performed at 1 and 2 weeks after inoculation. RESULTS: In BALB/c nude mice inoculated with Huh-7/hB7-1 cells, no tumor growth was observed. BALB/c nude mice inoculated with Huh-7/hB7-1 cells showed significantly increased NK cell activities of splenocytes compared with those with Huh-7/mock cells. Serum IFN-gamma was not measurable at 1 week, but significantly increased at 2 weeks after inoculation to the level of 470 pg/ml in BALB/c nude mice with Huh-7/mock cells and 521 pg/ml in BALB/c nude mice with Huh-7/hB7-1. CONCLUSIONS: Our results demonstrate the in vivo anti-tumor immunity and NK cell activation by transfer of hB7-1 gene into human HCC in xenogeneic BALB/c nude mice model. This approach may provide a tool for the development of immunogene therapies against human malignant tumors.
Asunto(s)
Animales , Humanos , Ratones , Antígeno B7-1/genética , Citotoxicidad Inmunológica , Técnicas de Transferencia de Gen , Interferón gamma/metabolismo , Células Asesinas Naturales/inmunología , Neoplasias Hepáticas Experimentales/genética , Ratones Endogámicos BALB C , Ratones Desnudos , Trasplante de NeoplasiasRESUMEN
Objective:To explore the action of the second signal system in the activatied and proliferating T cells and the induction of apoptosis of the hepatoma cells.Methods:The T cells were costimulated by anti CD28 and anti CD80(B7.1)McAb and acted on the hepatoma cells(BEL 7402),then testing the concentration of cAMP?cGMP and Ca 2+ in the T cells and the apoptosis of the hepatoma cells.Results:The concentration of cAMP was increased temporarily at first,then decreased rapidly,and increased 1 2 times again when acted on the hepatoma cells.The concentration of cGMP was increased 6 8 times fast and the concentration of Ca 2+ obviously increased 2 3 times too.The peak of them was at the fourth day and positive related to apoptosis of the hepatoma cells.Conclusion:The level of the second signal system of cAMP?cGMP and Ca 2+ were significant correlated with the T cells activated and porliferating and the cytotoxic effect.