Application of glycan microarrays in cancer research / 生物工程学报

Glycosylation is one of the common post-translational modifications of proteins to regulate the ability of tumor invasion, metastasis and tumor heterogeneity by interacting with glycan-binding proteins such as lectins and antibodies. Glycan microarray can be constructed by chemical synthesis, chemical-enzyme synthesis or natural glycan releasing. Glycan microarray is an essential analytical tool to discover the interaction between glycan and its binding proteins. Here we summarize the standard techniques to construct glycan microarray for the application in cancer vaccine, monoclonal antibody and diagnostic markers.

The epigallocatechin gallate derivative Y reverses drug resistance mediated by the ABCB1 transporter both and

Previously, we reported that Y, a new epigallocatechin gallate derivative, is efficacious in reversing doxorubicin (DOX)--mediated resistance in hepatocellular carcinoma BEL-7404/DOX cells. In this study, we evaluated the efficacy of Y in reversing drug resistance both and by determining its effect on the adenosine triphosphate-binding cassette protein B1 transporter (ABCB1 or P-glycoprotein, P-gp). Our results showed that Y significantly sensitized cells overexpressing the ABCB1 transporter to anticancer drugs that are ABCB1 substrates. Y significantly stimulated the adenosine triphosphatase activity of ABCB1. Furthermore, Y exhibited a higher docking score as compared with epigallocatechin gallate inside the transmembrane domain of ABCB1. In addition, in the nude mouse tumor xenograft model, Y (110 mg/kg, intragastric administration), in combination with doxorubicin (2 mg/kg, intraperitoneal injection), significantly inhibited the growth of BEL-7404/DOX cell xenograft tumors, compared to equivalent epigallocatechin gallate. In conclusion, Y significantly reversed ABCB1-mediated multidrug resistance and its mechanisms of action may result from its competitive inhibition of the ABCB1 drug efflux function.

Clinical analysis on platinum-based combined chemotherapeutical regimens for treating relapsed or refractory non-Hodgkin lymphoma / 重庆医学

Objective To evaluate the efficacy and adverse reactions of platinum-based combined chemotherapeutical regimens in treating relapsed or refractory non-Hodgkin lymphoma(NHL).Methods The clinical data of 68 patients with relapsed or refractory NHL treated with platinum-based combined chemotherapeutical regimens in the Affiliated Tumor Hospital of Guangxi Medical University from January 2008 to December 2014 were retrospectively analyzed.The curative effect of related regimens,adverse reactions and related influence factors were analyzed.Results Sixty-eight cases received 283 cycles of chemotherapy.In all cases,11 cases(16.18 ％) achieved the complete response(CR),31 cases(45.59 ％) achieved the partial response(PR),the overall response rate(ORR) was 61.76％;the median progression-free survival(PFS) was 6.51 months(95％CI:4.97-8.04 months).ORR and PFS in the cases of stage Ⅱ-Ⅲ,IPI score 0-2 and receiving only one chemotherapeutical regimen were superior to those in the cases of corresponding subgroup(P＜0.05);ORR and PFS had no statistical difference between the B cells lymphoma and Tcells lymphoma(P＞0.05).The medion PFS in the combined R group was 11.16 months,which was longer than 5.84 months in the non-combined R group(P =0.004).The major adverse events (stage Ⅱ-Ⅲ) included leukopenia (41.18 ％),thrombocytopenia (27.94％),hemoglobin decrease(11.76％),vomiting(8.82％) and diarrhea(1.47％).Conclusion The platinum-based combined chemotherapeutical regimens are effective with good safety in the treatment of relapsed or refractory NHL.

Relationship of PLXNC1 (rs2272335) polymorphism with genetic susceptibility to primary liver cancer among family clusters in Guangxi and its expression / 中国肿瘤临床

Objective:To investigate the correlation between plexinC1 (PLXNC1) rs2272335 polymorphism and the family clus-tering genetic susceptibility to primary liver cancer (PLC) in Guangxi and the expression of PLXNC1. Methods:Genotype and alleles of rs2272335 were determined in 20 liver cancer family groups (79 cases) and 10 healthy normal control groups (40 cases) in Fusui County through Time of Flight Mass Spectrometer. Immunohistochemistry detected the PLEXNC1 protein expression. Results:For the alleles of PLXNC1 (rs2272335) site, the risk of hepatocellular carcinoma (HCC) for individuals with [C] allele was 4.16-fold (95%CI=0.37-47.3, P=0.032) compared with that for individuals with [T] allele among the members of the healthy normal control group. The fre-quencies of the [C] and [T] alleles were similar in the HCC patients and the core individuals of liver cancer families (P>0.05). For the genotype of the PLXNC1 (rs2272335) site, the differences in frequencies of TT, TC, and CC genotypes were not statistically significant among the PLC patients and the core individuals of the liver cancer families and normal controls. The PLXNC1 protein expression in HCC (3.12±1.12) was higher than in hepatocellular paracancerous tissues (1.54±0.67) and in benign hepatocellular lesions (1.23±0.87) (P<0.05). Conclusion:The [C] allele of PLXNC1 (rs2272335) site might be the risk gene for the occurrence of PLC family clustering in Guangxi. PLXNC1 protein overexpression was closely correlated with PLC oncogenesis.

Effects of hMIP-1beta gene modification on in vivo tumorigenicity and vaccine efficacy of tumor cells / 中华肿瘤杂志

<p><b>UNLABELLED</b>OBJECTIVE To explore the effects of human macrophage inflammatory protein-1 beta (hMIP-1beta) modification on the in vivo tumorigenicity and vaccine efficacy of tumor cells.</p><p><b>METHODS</b>Murine colorectal adenocarcinoma CT26 cells were transfected with a recombinant adenovirus carring the hMIP-1beta gene (AdhMIP-1beta). The efficacy of gene transfection was tested by X-gal staining. The hMIP-1beta level in the supernatant of hMIP-1beta gene-modified CT26 cells was assayed by ELISA, and the chemotactic activity for CD4+ T cells, CD8+ T cells, NK cells and immature dendritic cells (imDCs) were assayed by a transwell chamber. The changes of growth characteristics and in vivo tumorigenicity of hMIP-1beta gene-modified CT26 cells were also assessed. BALB/c mice were immunized with hMIP-1beta gene-modified CT26 tumor vaccine and the antitumor effect was evaluated.</p><p><b>RESULTS</b>hMIP-1beta gene could be transfected into CT26 cells by AdhMIP-1beta with an efficiency over 95%. The level of hMIP-1beta in the culture supernatant of hMIP-1beta gene-modified CT26 cells was 980 pg/ml and the supernatant displayed ramarkable chemotactic activity to CD4+ T cells, CD8+ T cells, NK cells and imDCs compared with LacZ gene-modified CT26 cells and control. When the hMIP-1beta gene-modifited CT26 cells were subcutaneously inoculated in BALB/c mice, the tumorigencity was delayed and suppressed, and overt necrosis and lymphocyte infiltration were observed in the tumor tissue, but not in those inoculated with LacZ gene-modified CT26 cells or parental CT26 cells. The mice immunized with hMIP-1beta gene-modified CT26 tumor vaccine could induce tumor specific CTL activity and nonspecific NK activity, and exhibited resistance to later challenge with wild-type CT26 cells.</p><p><b>CONCLUSION</b>hMIP-1beta gene-modified CT26 cells exhibit decreased tumorigenicity, and hMIP-1beta gene-modified tumor vaccine may induce a powerful specific and nonspecific antitumor response. The data suggested that hMIP-1beta gene-modified tumor vaccine may play a potent role in prevention of metastasis and recurrence of malignant tumors.</p>

Dendritic cell vaccine modified by murine mAFP gene enhances immunoprotective effect on liver carcinogenesis and tumor development in mice / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To construct a dendritic cell vaccine transduced by murine alpha-fetoprotein (mAFP) gene, and evaluate its immunoprotective effect on C57BL/6J mice during the induction of hepatocellular carcinoma by diethylnitrosamines, carbon tetrachloride and ethanol.</p><p><b>METHODS</b>Dendritic cells (DCs) were induced and augmented by murine IL-4 and GM-CSF, and transfected by recombinant adenovirus engineered with mAFP gene. Major MHC class I and II, B7.1 (CD80), B7.2 (CD86), CD18a, and CD54 molecules on DC were analyzed by FACS. 80 C57BL/6J male mice were randomly divided into 4 groups (20 mice per group): Simple DC inoculated group, pAdBM5-mAFP-DC inoculated group, pAdBM5-mAFP plasmid inoculated group, and PBS control group. They were immunized once with 5 x 10(5) DCs (0.1 ml)/mouse administered s. c. in the left flank or 100 mg pAdBMS-mAFP plasmid/mouse administered i. m. in the left tibialis anterior muscle. Inoculation was conducted once a week for 4 weeks after 3 times consecutive immunization initially. At the same time of immunization, DEN/CCl4/ethanol were given to induce hepatocellular carcinoma. Tumor incidence was assessed after 20 weeks.</p><p><b>RESULTS</b>A transgenic DC vaccine was successfully constructed and the mAFP transgenic DCs expressed high level molecules of major MHC class I and II , B7.1, B7.2, CD18a, and CD54. After the 20-week induction, the incidence of primary hepatocellular carcinoma (PLC) was 70.0% in simple DC inoculated group, 25.0% in pAdBMS-mAFP-DC inoculated group, 65.0% in pAdBM5-mAFP plasmid inoculated group, and 75.0% in PBS control group. There was a significant difference between group B and other groups (P < 0.05).</p><p><b>CONCLUSION</b>mAFP transgenic DC tumor vaccine inoculation may induce strong immunoprotection against liver carcinogenesis and tumor development and reduce PLC incidence induced by DEN/CCl4/ethanol.</p>