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ERBB Signaling Pathway Targeted Therapy Is Available in Gallbladder Cancer Patients
( Xu’an Wang ),( Maolan Li ),( Xiangsong Wu ),( Ping Dong ),( Wei Gong ),( Yingbin Liu ) 대한간학회 2018 춘·추계 학술대회 (KASL) Vol.2018 No.1
Aims: To profile the somatic mutation spectrum in gallblad der cancers(GBCs), to determine the oncogenic effects of the ERBB3 and ERBB2 mutations, and to find whether targeted therapy focus on ERBB signaling pathway is available for these kind of GBC patients. Methods: We performed a combination of exome sequencing and ultra-deep sequencing of cancer-related genes on 57 tu mor-normal pairs. The mutation pattern is defined by a domi nant prevalence of C>T mutations at TCN sites.Three patients with staged IV GBCs and ERBB signaling pathway mutated who were not benefit from traditional chemo-radio therapy, were treated with ERBB signaling pathway targeted therapy. Results: Genes with a significant frequency of non-silent muta tions include TP53 (47.1%), KRAS (7.8%) and ERBB3 (11.8%). Moreover, ErbB signaling (including EGFR, ERBB2, ERBB3, ERBB4 and their downstream genes), which have not been described previously in GBC, is the most extensively mutated pathway, affecting 36.8% (21/57) of the GBC samples. Multi variate analyses further show that the mutations have a worse outcome. Over-expression of each ERBB mutant resulted in a significant increase in proliferation in at least one cell line.The tumor maker expression including CA-199 and CA-125 had a different level of decline.The primary or metastasis tumor size also revealed a trend of decrease. And the average survival time have exceeded more than 12months. Conclusions: Our findings provide insight into the somatic mutational landscape in GBC and highlight the key role of the ErbB signaling pathway in GBC pathogenesis.And our results suggest that patients harboring mutations in the ErbB pathway might benefit from targeted therapies.
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Zu-Quan Hu,He-Ping Li,Jin-Long Liu,Sheng Xue,An-Dong Gong,Jing-Bo Zhang,Yu-Cai Liao 한국생물공학회 2016 Biotechnology and Bioprocess Engineering Vol.21 No.1
Fumonisins produced by Fusarium pathogens are mycotoxins present in maize and other grains in the field as well as during storage worldwide and pose a serious threat to humans and domestic animals. Fumonisin B consists of different chemotypes, and fumonisin B1 (FB1) is the most predominant fumonisin found in food/feed commodities. Recombinant antibody can be deployed to analyze the fumonisin toxicological mechanism and develop a simple and cost-effective method for the detection of fumonisins, which is vitally important for monitoring and preventing fumonisins from entering food/feed chains. In this study, FB1 conjugated to keyhole limpet hemocyanin was used to immunize mice, from which RNA was isolated to construct a recombinant antibody library. Successive panning of the library by phage display was used to select monoclonal phage clones reactive to FB1 conjugated to bovine serum albumin. Subsequent phage ELISA and sequencing analyses revealed four different reactive scFv antibodies specific to FB1. Soluble expression and ELISA analysis showed that one scFv antibody, FBMA1, had the highest reactivity and could be purified from bacterial cells in large quantities. Surface plasmon resonance measurements further revealed that the FBMA1 scFv antibody had a binding kinetics of KD = 1.89 × 10–7 M. Molecular modeling and docking analyses suggested that the FBMA1 antibody shaped a proper cavity to embed the whole FB1 molecule and that a steady-state complex was formed relying on intermolecular forces, including hydrogen bonding, electrostatic force and hydrophobic interactions. Thus, the scFv antibody can be applied for mechanistic studies of intermolecular interactions and fumonisin toxicity, and for the development of an immunoassay for fumonisin-contaminated food/feed samples.
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