We have previously described two monoclonal antibodies,anti-CCT1 and antiCCT3,which recognize TP50 protein(associated with E-receptor)on human T cell surface.In this paper,the results of further studies on the determinants the two monolonal antibodies recognize and their functions are presented.anti-CCT3 blocked E rosette formation but anti-CCT1 did not.However,CCT1 and CCT3 determinantscould be.co-modulated by both monoclonal antibodies.When T cells were treated withboth antibodies simultaneously,the indirect immunofluorescence revealed by cytofluo-rograf was additive.Functionally,anti-CCT1 and anti-CCT3 were similar.Bothinhibited the proliferative response of peripheral blood lynphocyte to PHA and theexpression of IL-2 receptor.These results indicate that CCT1 and CCT3 are twodifferent epitopes on the TP50 molecules and are functionelly involved in the pro-liferation of T cells in response to mitogens.

OBJECTIVE:To study the incidence,types,constitution ratio of adverse drug reactions(ADR)induced by antibiotics and the correlation factors of the ADR so as to promote rational drug use in our hospital.METHODS:The literature about antibiotics-induced ADR from Jan.1980 to May 2008 retrieved from CNKI,Wanfang Data and VIP full-text data base was analyzed quantitatively by dividing the literature into different categories:case study or typical case reports,clinical trial or observational reports,and regional ADR monitoring data base or hospital ADR analytical reports.RESULTS:There were 2 310 case studies or typical case reports and in which 3 794 ADR cases were reported,which manifested chiefly as allergic reaction(35.58%),nervous system reaction(17.82%)and disulfiram-like reaction(in 546 cases).928 papers were literature about clinical trial or observational reports and in which 9 434 ADR cases were reported and the average ADR incidence was 9.14%,with anti-tuberculosis drugs showing the highest proportion(25.57%),followed by nitromidazole(24.29%)and carbapenem antibiotics(23.52%);and the ADR manifested chiefly as gastrointestinal tract reaction and allergic reaction,and there were ADR cases manifested as pathoglycemia induced by quinolones.There were 300 papers were literature about regional ADR monitoring data base or hospital ADR analytical reports,in which almost all the major variety of antibiotics were involved,leading the list in terms of ADR cases were quinolones,penicillins and cephalosporins.CONCLUSION:Great importance should be attached to the rational use of antibiotics so as to avoid or reduce ADR incidence and ensure safe and effective use of antibiotics in patients.

In recent years, with the advances in life cycle of hepatitis C virus (HCV) and the approval of direct-acting antiviral agents (DAAs), great progress has been made in treatment of chronic hepatitis C (CHC).This article reviews the research progress of DAAs in CHC management, showing the possibility of the elimination of HCV infection by DAAs.DAAs have not been widely clinically used due to high medication costs, but can be used as a supplement for the combination therapy of pegylated interferon and ribavirin.

There are about 150 million people around the world with chronic hepatitis C virus (HCV)infection currently,of whom 20%will ultimately progress to cirrhosis and eventually die of end-stage liver disease and hepatocellular carcinoma.Interferon (IFN)has long been recognized as the cornerstone of the treatment of chronic hepatitis C because of its role in sustained virologic response and prevention of disease progression.However,it has limited efficacy and multiple adverse effects.In recent years,direct-acting antiviral agents (DAAs) have shown good efficacy.This review summarizes the recent advances in IFN-free anti-HCV therapeutic regimens based on DAAs.We believe that,with the emergence of DAAs,IFN-free therapies will develop rapidly and display better prospects.

Objective To make use of the characteristics of presenting and processing tumor antigen of dendritic cells to enhance killing capability of CTLs against autologous renal cell carcinoma. Methods Autologous dendritic cells were obtained by culturing bone marrow cell from patient with RCC in the presence of granulocyte macrophage colony stimulating factor(GM CSF) and IL 4. Dendritic cells were loaded with tumor cell lysate and co cultured with autologous PBMCs from patient to induce generation of tumor specific cytotoxic T cells(CTL). Killing activity and cytokine release of the CTL and the population of CTL were measured by cytotoxic assay and ELISA and FACS analyses. Results Immune response of DC Tuly induced CTL was demonstrated by the following facts:(1)the growth expansion of CTL enhanced 43 folds on day 16;(2)up regulation of the CD3 + and CD8 + population in CTL;(3)the cytotoxicity of specific CTL against autologous RCC was highly enhanced as compared with allogenic RCC and heterogenous tumor( P

Objective To establish human renal cell carcinoma (RCC) cell lines,and to investigate the cell phenotypes and expression of tumor associated antigens. Methods Fresh tumor tissues from pathologically proven human RCCs were primary cultured and passed generation to generation until a stably grow in vitro.The cell cloning form,chromosome and graft into nude mice in vivo were examined for cell lines.Immunofluorescent stain and flow cytometric analysis were carried out for cell's phenotype,RT PCR examination for MN/CA9 gene expression. Results Six human RCC cell lines have been established,including four of the cell lines derived from clear cells,one from mixed clear granular cells and one from papillary cells.All the cell lines showed the characteristics of malignant cells.All the lines highly expressed HLA ClassⅠ and HER2/neu.Three lines weakly expressed HLA ClassⅡ and one cell line highly expressed CD86 but all the lines did not express CD80.RT PCR showed that three cell lines have the expression of MN/CA9 gene. Conclusions These newly established RCC cell lines would provide a useful in vitro model for studies related to biological characteristics,tumor associated antigen,immunogenity and immunotherapy of human RCC.

ObjectiveTo provide experimental proof for the specific immunotherapy in patients with renal cell carcinoma (RCC).MethodsThe expression of c-erbB-2 and HLA-A2 molecules in RCC were examined by flow cytometery and HLA-A2 cDNA RT-PCR.Tumor lysatic antigens (Tuly) was used to load DCs (DC-Tuly) to induce the generation of c-erbB-2 specific CTLs derived from peripheral blood mononuclear cells of RCC patients in vitro and CTLs was used to kill RCC cells which express or not express c-erbB-2 and HLA-A2.The cytotoxic activity of induced CTLs was further studied by antibodies (anti-c-erbB-2 and anti-CD 8) blocking assay.Resultsc-erbB-2 protein is tumor associated antigens for RCC.DC-Tuly induced specific CTLs highly killed c-erbB-2+ HLA-A2+ autologous and allogenic RCC,but non-specific ones lowly killed c-erbB-2- HLA-A2+ or c-erbB-2+ HLA-A2-RCC cells. The cytotoxic activity against tumor cells was blocked by anti-c-erbB-2 and anti-CD 8 monoclonal antibodies.ConclusionsThese results suggest that this specific CTLs adoptive immunotherapy for RCC patients with c-erbB-2+ HLA-A2+ could be a novel approach for clinical use.

Objective:To investigate the inducing effects of sunitinib malate on expression of NKG2D ligands in nasopharyngeal carcinoma cell ABCG2high CNE2/DDP.Methods:ABCG2highCNE2/DDP cells and Allo-NK cells were isolated by magnetic activated cell sorting(MACS).Flow cytometry was used to evaluate the purity of isolated cells and the expression of NKG2D-ligands on target cells before and after incubation with sunitinib malate.Then the cytotoxic sensitivity of treated and un-treated ABCG2high CNE2/DDP cells to Allo-NK cells were measured by LDH releasing assay.Results:The positive rate of ABCG2 in ABCG2highCNE2/DDP cells was(91.40?2.32)%.More than 90% of isolated Allo-NK cells were proven to be CD3-CD16+CD56+ cells.The expression of MICA,MICB,ULBP1,ULBP2 and ULBP3 on ABCG2high CNE2/DDP cells incubated with sunitinib malate increased from(2.92?0.33)%,(4.27?0.33)%,(5.80?0.62)%,(11.10?3.15)%,and(7.75?1.14)% to(89.12?4.56)%,(66.10?2.22)%,(67.56?4.19)%,(69.37?8.83)%,and(63.28?3.31)%,respectively.At the E ∶T ratios of 10 ∶1 and 20 ∶1,the cytotoxic sensitivities of ABCG2high CNE2/DDP cells to Allo-NK cells increased from(15.32?13.86)% and(27.26?6.81)% to(41.12?4.12)% and(57.25?2.37)%,respectively,after treatment with sunitinib malate,with significantly difference found in the cytotoxic sensitivities of target cells in each group before and after sunitinib malate treatment(F=15.58,P=0.000).Conclusion:Sunitinib malate can up-regulate expression of NKG2D-ligands(MICA/B,ULBP1-3)in ABCG2high nasopharyngeal carcinoma cells,which results in higher cytotoxic sensitivity to Allo-NK cells.

Interferon and nucleotide/nucleoside analogues are currently widely used in the management of chronic hepatitis B virus ( HBV) infections, but are facing problems such as poor sustained virologic response, low HBsAg clearance rate and a high risk of recurrence after drug withdraw.Exploring new target of anti-HBV agent has become a hot topic in recent years.This paper reviews the research progress on new anti-HBV targets and related drugs.

Objective To investigate the association of restriction fragment length polymorphisms (RFLP) in p.S267F of SLC10A1 gene with clinical outcomes of hepatitis B virus (HBV) infection. Methods Clinical data of 1 268 patients with HBV infections admitted in Public Health Clinical Center Affiliated to Fudan University during July 2014 and February 2015 were collected.Polymerase chain reaction-restriction fragment length polymorphism ( PCR-RFLP) method was used to genotype the p .S267F of SLC10A1 gene in all patients, and the potential association between variants in p .S267F of SLC10A1 gene and the clinical outcomes of HBV infection was analyzed .Results Among 1 268 patients with HBV infections, 1 226 were of genotype CC, and 42 were of genotype CT, so the variation rate in p.S267F was 3.31%(42/1 268).Compared with patients with genotype CC , patients with genotype CT had a higher incidence of acute HBV infections (13.6%vs.28.6%,χ2 =19.819, P<0.05) and a lower incidence of HBV-related liver cirrhosis or hepatocellular carcinoma (13.9% vs.4.8%, χ2 =18.945, P <0.05). Conclusion RFLP in p.S267F of SLC10A1 gene may be associated with chronicity and aggravation of HBV infection, and genotype CT is possibly a protective factor .