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Xu J.,Shanghai Zhangjiang Biotechnology Co. | Xu J.,Fudan University | Zhang D.,Shanghai Zhangjiang Biotechnology Co. | Zhang D.,State Key Laboratory of Antibody Medicine and Targeted Therapy | And 4 more authors.
Shengwu Gongcheng Xuebao/Chinese Journal of Biotechnology | Year: 2016

We compared the similarity of Omalizumab (Xolair; a humanized anti-immunoglobulin E monoclonal antibody) and it's biosimilar CMAB007. An in depth characterization of a candidate biosimilar was carried out using a systematic approach, the approach provides a set of routine tools that combine accurate intact mass measurement, peptide mapping, and released glycan profiling. CMAB007 and Omalizumab had the same primary structure and exhibited almost the same content of C-terminal lysine variants. The types of detected free oligosaccharides were very similar, such as sialylation, fucosylation and high mannose types. CMAB007 could be considered as a highly similar molecular to Omalizumab and expected to be the first humanized anti-immunoglobulin E monoclonal antibody drug in China. © 2016 Chin J Biotech, All right reserved. Source

Liu T.,International Medical University | Guo Q.,International Medical University | Guo Q.,State Key Laboratory of Antibody Medicine and Targeted Therapy | Guo H.,International Medical University | And 6 more authors.
Biomedical Chromatography | Year: 2016

The epigenetic remodeling of chromatin through histone modifications has been widely implicated in drug resistance of cancer cells. However, whether epigenetic mechanisms contribute specifically to doxorubicin resistance in leukemia has not been carefully examined. Using a stable and sensitive workflow based on LC-MS, we quantitatively compared the extents of methylation and acetylation of histone H3 and H4 in acute leukemia cell line HL60 and its doxorubicin-resistant derivative, HL60/ADR, as well as the chronic leukemia cell line K562 and its doxorubicin-resistant derivative, K562/ADR. We found that increased levels of H3K9 methylation, H3K14, H3K18 and H3K23 acetylation, and potentially H4K20 methylation, are associated with drug resistance in both cells. Our results demonstrated that the doxorubicin-resistant acute and chronic leukemia cell lines may share a common epigenetic mechanism that involves a combination of transcriptional activation and silencing. © 2016 John Wiley & Sons, Ltd. Source

Li J.,International Medical University | Huang K.L.,Washington University in St. Louis | Zhang T.,International Medical University | Li H.,International Medical University | And 7 more authors.
Neoplasma | Year: 2016

Adenocarcinomas are tumors of glandular characteristics. While tissues of common origins have been known to undergo similar epigenetic changes, it is unclear whether adenocarcinomas of different cancer types would exhibit similar DNA methylation and epigenetic regulation profiles. Herein, we studied global methylation and mRNA expression levels in 1214 lung, prostate, colon, and rectal cancer samples from The Cancer Genome Atlas (TCGA). We identified 602 candidate epigenetically silenced genes shared across these cancer types, and 835 associated CpG sites. The shared candidate genes are enriched in developmental processes. Specifically, 15 of these genes were found in the WNT signaling pathway (enrichment test p-value=1.53×10-6). Notably, the subset of silenced WNT pathway genes in each sample may be different, and both WNT activating or inhibiting genes could be suppressed. Clustering analysis showed that each tumor type contained a similar hyper-methylated subset of samples showing strong epigenetic silencing in the WNT pathway genes, and other fractions of samples expressing subset of the genes. Overall, our results showed that aberration in epigenetic regulation of the WNT signaling pathway is a common signature in adenocarcinomas. © 2016, Cancer Research Institute Slovak Acad. of Sciences. All rights reserved. Source

Han S.,General Hospital Cancer Center | Han S.,Liaocheng University | Meng Y.,Nankai University | Meng Y.,Liaocheng University | And 23 more authors.
mAbs | Year: 2014

The anti-ErbB2 antibody trastuzumab has shown significant clinical benefits in ErbB2-overexpressing breast and gastric cancer, but resistance to the drug is common. Here, we investigated the antitumor activity of the combination of trastuzumab and the SRC inhibitor saracatinib in ErbB2-overexpressing trastuzumab-resistant gastric cancer. The ErbB2-overexpressing human gastric cancer cell line NCI-N87 was treated with trastuzumab to obtain the trastuzumab-resistant cell line NCI-N87R. The NCI-N87R cell line showed a marked increase in SRC activity and ErbB signaling compared with the NCI-N87 cell line. Our data demonstrated that trastuzumab plus saracatinib was much more potent than either agent alone in reducing the phosphorylation of ErbB3 and AKT in both NCI-N87 and NCI-N87R gastric cancer cell lines. Trastuzumab and saracatinib synergistically inhibited the in vitro growth of NCI-N87 and NCI-N87R cell lines. Further data showed that combination therapy of trastuzumab with saracatinib resulted in a significant benefit over either agent alone in both NCI-N87 and NCI-N87R xenograft models, suggesting its potential use for treating ErbB2-overexpressing gastric cancer. © 2014 Landes Bioscience. Source

Deng Y.-Q.,Beijing Institute of Microbiology and Epidemiology | Dai J.-X.,International Medical University | Dai J.-X.,State Key Laboratory of Antibody Medicine and Targeted Therapy | Ji G.-H.,International Medical University | And 13 more authors.
PLoS ONE | Year: 2011

Flaviviruses are a group of human pathogenic, enveloped RNA viruses that includes dengue (DENV), yellow fever (YFV), West Nile (WNV), and Japanese encephalitis (JEV) viruses. Cross-reactive antibodies against Flavivirus have been described, but most of them are generally weakly neutralizing. In this study, a novel monoclonal antibody, designated mAb 2A10G6, was determined to have broad cross-reactivity with DENV 1-4, YFV, WNV, JEV, and TBEV. Phage-display biopanning and structure modeling mapped 2A10G6 to a new epitope within the highly conserved flavivirus fusion loop peptide, the 98DRXW101 motif. Moreover, in vitro and in vivo experiments demonstrated that 2A10G6 potently neutralizes DENV 1-4, YFV, and WNV and confers protection from lethal challenge with DENV 1-4 and WNV in murine model. Furthermore, functional studies revealed that 2A10G6 blocks infection at a step after viral attachment. These results define a novel broadly flavivirus cross-reactive mAb with highly neutralizing activity that can be further developed as a therapeutic agent against severe flavivirus infections in humans. © 2011 Deng et al. Source

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