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Gong Chen, Ya-Chi Chen, Bernhard Reis, Anton Belousov, Lori Jukofsky, Christine Rossin, Axel Muehlig, Chao Xu, Laurent Essioux, Toshihiko Ohtomo, Laura Di Laurenzio, Oscar Puig, Ray Lee
Background: Codrituzumab, a monoclonal antibody targeting an oncofetal protein glypican-3 (GPC3) expressed on cell surface of hepatocellular carcinoma (HCC) induces antibody-dependent cellular cytotoxicity (ADCC) and inhibits tumor growth in preclinical studies. Based on this mechanism, tumor GPC3 expression and CD16 expression on NK cells, which are the effector cells of ADCC, were investigated to correlate with codrituzumab's clinical efficacy in patients with advanced HCC. Results: Joint analyses of the two biomarkers revealed that both high levels of GPC3 and CD16 were required for patients to benefit from codrituzumab; lack of either one of them would lead to a loss of the therapeutic effect...
February 13, 2018: Oncotarget
Xiao Rui
The detection of hepatocellular carcinoma (HCC) circulating tumor cells (CTCs) from a blood sample can be a very powerful noninvasive approach for the early detection and therapy of liver cancer. However, the extremely rare cells in blood containing billions of other cells make the capture and identification of CTCs with sufficient sensitivity and specificity a real challenge. Here, a magnetically assisted surface-enhanced Raman scattering (SERS) biosensor for HCC CTCs detection is reported for the first time...
March 9, 2018: Chemistry: a European Journal
Shanshan Zhong, Yang Zhao, Chuifeng Fan
RATIONALE: Hepatoblastoma is a rare malignant embryonal tumor that only accounts for approximately 1% of all pediatric cancers and mostly develops in children younger than 5 years old. Moreover, the occurrence of hepatoblastoma in adults is extremely rare. PATIENT CONCERNS: Herein, we present a rare case of hepatoblastoma with pure epithelial differentiation in a 10-year-old boy.Pathological examination was performed. The tumor was 15 cm × 15 cm in size with clear margins...
January 2018: Medicine (Baltimore)
You-Cai Li, Chuan-Sheng Yang, Wen-Lan Zhou, Hong-Sheng Li, Yan-Jiang Han, Quan-Shi Wang, Hu-Bing Wu
AIM: To investigate the relationship between glucose metabolism and glypican-3 (GPC3) expression in hepatocellular carcinoma (HCC). METHODS: Immunohistochemical staining of pathological samples for GPC3 and glucose transporter 1 (GLUT1), and whole-body 18F-FDG PET/CT for measuring tumour glucose uptake were performed in 55 newly diagnosed HCC patients. The maximum standard uptake value (SUVmax) and tumour-to-non-tumourous liver uptake (T/NT) ratio were used to quantify 18F-FDG uptake...
January 28, 2018: World Journal of Gastroenterology: WJG
Qingyu Shen, Suk Woo Nam
An accurate diagnostic marker for detecting early-stage hepatocellular carcinoma (eHCC) is clinically important, since early detection of HCC remarkably improves patient survival. From the integrative analysis of the transcriptome and clinicopathologic data of human multi-stage HCC tissues, we were able to identify barrier-to-autointegration factor 1 (BANF1), procollagen-lysine, 2-oxoglutarate 5-dioxygenase 3 (PLOD3) and splicing factor 3b subunit 4 (SF3B4) as early HCC biomarkers which could be detected in precancerous lesions of HCC, with superior capabilities to diagnose eHCC compared to the currently popular HCC diagnostic biomarkers: GPC3, GS, and HSP70...
February 5, 2018: BMB Reports
Hui Xie, Yao-Qin Xue, Peng Liu, Peng-Jun Zhang, Sheng-Tao Tian, Zhao Yang, Zhi Guo, Hua-Ming Wang
AIM: In our previous study, we have built a nine-gene (GPC3, HGF, ANXA1, FOS, SPAG9, HSPA1B, CXCR4, PFN1, and CALR) expression detection system based on the GeXP system. Based on peripheral blood and GeXP, we aimed to analyze the results of genes expression by different multi-parameter analysis methods and build a diagnostic model to classify hepatocellular carcinoma (HCC) patients and healthy people. METHODS: Logistic regression analysis, discriminant analysis, classification tree analysis, and artificial neural network were used for the multi-parameter gene expression analysis method...
January 21, 2018: World Journal of Gastroenterology: WJG
Mikiko Nakamura, Chao Xu, Cheikh Diack, Norihisa Ohishi, Ruey-Min Lee, Satofumi Lida, Takehiko Kawanishi, Toshihiko Ohtomo, Ghassan K Abou-Alfa, Ya-Chi Chen
AIMS: Codrituzumab (GC33) is a recombinant, humanized mAb that binds to glypican-3 (GPC3), an oncofoetal protein highly expressed in hepatocellular carcinoma (HCC). This investigation aimed to identify clinically relevant factors that may affect the overall survival (OS) in HCC patients treated with codrituzumab and to quantitatively annotate their effects. METHODS: Codrituzumab exposure was estimated by a population pharmacokinetics model with a non-linear elimination pathway...
January 30, 2018: British Journal of Clinical Pharmacology
Pei Hu, Bin Cheng, Yulin He, Zhiqiang Wei, Dongfang Wu, Zhongji Meng
Introduction: Autophagy plays an important role in the growth and survival of hepatocellular carcinoma (HCC) cells through several target proteins or signaling pathways. Glypican-3 (GPC3) is a new reliable HCC marker, which is involved in tumor growth in HCC, primarily mediated by wnt/β-catenin signaling. Objective: The present study aimed to identify the role of autophagy in the proliferation of HepG2 cells through GPC3/wnt/β-catenin signaling. Results and discussion: Results demonstrated that induction of autophagy by nutrition starvation and rapamycin treatment led to the downregulation of GPC3 expression in HepG2 cells, accompanied by the decreased expression of wnt downstream target genes (β-catenin, c-myc and cyclin D1)...
2018: OncoTargets and Therapy
Hong Liu, Chunmei Yang, Wenzhu Lu, Yong Zeng
BACKGROUND: In recent years, an increasing number of studies has been published analyzing the possible prognostic utility of glypican-3 (GPC3) in hepatocellular carcinoma (HCC), but the results are still controversial. The aim of this meta-analysis was to evaluate possible association between GPC3 expression and patients' survival. METHODS: Relevant publications which assessed GPC3 expression with survival outcome in HCC patients were searched from Pubmed, Embase, Web of Science, and the Cochrane library...
January 2018: Medicine (Baltimore)
Ahmad Saad, Benjamin Liet, Gilles Joucla, Xavier Santarelli, Justine Charpentier, Stéphane Claverol, Christophe F Grosset, Véronique Trézéguet
Glypican 3 (GPC3) is a complex heparan sulfate proteoglycan associated with the outer surface of the plasma membrane by a glycosyl-phosphatidylinositol anchor (GPI). It is also N-glycosylated and processed by a furine-like convertase. GPC3 has numerous biological functions. While undetectable in normal liver tissue, it is abnormally and highly overexpressed in hepatocellular carcinoma (HCC). Interestingly, proliferation of HCC cells such as HepG2 and HuH7 is inhibited when they express a soluble form of GPC3 after lentiviral transduction...
January 18, 2018: Biochemistry
Min Yu, Hong Luo, Mingliang Fan, Xiuqi Wu, Bizhi Shi, Shengmeng Di, Ying Liu, Zeyan Pan, Hua Jiang, Zonghai Li
Chimeric antigen receptor (CAR)-modified natural killer (NK) cells represent a promising immunotherapeutic modality for cancer treatment. However, their potential utilities have not been explored in hepatocellular carcinoma (HCC). Glypian-3 (GPC3) is a rational immunotherapeutic target for HCC. In this study, we developed GPC3-specific NK cells and explored their potential in the treatment of HCC. The NK-92/9.28.z cell line was established by engineering NK-92, a highly cytotoxic NK cell line with second-generation GPC3-specific CAR...
December 19, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
Sarah E Woodfield, Yan Shi, Roma H Patel, Jingling Jin, Angela Major, Stephen F Sarabia, Zbigniew Starosolski, Barry Zorman, Siddharth S Gupta, Zhenghu Chen, Aryana M Ibarra, Karl-Dimiter Bissig, Ketan B Ghaghada, Pavel Sumazin, Dolores López-Terrada, Sanjeev A Vasudevan
Currently, preclinical testing of therapies for hepatoblastoma (HB) is limited to subcutaneous and intrasplenic xenograft models that do not recapitulate the hepatic tumors seen in patients. We hypothesized that injection of HB cell lines into the livers of mice would result in liver tumors that resemble their clinical counterparts. HepG2 and Huh-6 HB cell lines were injected, and tumor growth was monitored with bioluminescence imaging (BLI) and magnetic resonance imaging (MRI). Levels of human α-fetoprotein (AFP) were monitored in the serum of animals...
December 19, 2017: Scientific Reports
Karen Chong, Maha Saleh, Marie Injeyan, Ioana Miron, Katherine Fong, Patrick Shannon
OBJECTIVE: Congenital diaphragmatic hernia (CDH) is associated with Simpson-Golabi-Behmel syndrome (SGBS), but few cases diagnosed prenatally have been reported. The aim of this series is to highlight the association of non-isolated CDH with SGBS type I on prenatal ultrasound and emphasize the importance of genetic testing, fetal autopsy and family history in confirming this diagnosis. METHOD: Retrospective review of three cases of SGBS type I in a single tertiary care centre...
December 14, 2017: Prenatal Diagnosis
Ji-Sheng Jing, Wei Ye, Ying-Kui Jiang, Jie Ma, Meng-Qi Zhu, Jiu-Ming Ma, Hua Zhou, La-Qing Yu, Yong-Feng Yang, Shun-Cai Wang
BACKGROUND: The incidence of hepatocellular carcinoma (HCC) has increased over the past decades in China. Current screening methods of HCC such as detection of α-fetoprotein (AFP) combined with liver ultrasonography remain unsatisfactory. Many HCC patients have already missed the optimal treatment period when diagnosed. Our study aimed to evaluate the value of Glypican 3 (GPC3) and Golgi protein 73 (GP73) in the detection of HCC. METHODS: Thirty-nine patients with HCC and 31 patients with liver cirrhosis were enrolled...
November 1, 2017: Clinical Laboratory
Mauro Montalbano, Cristiana Rastellini, Joshua T McGuire, Janika Prajapati, Ali Shirafkan, Renza Vento, Luca Cicalese
BACKGROUND: Recently, Glypican-3 (GPC3) has been identified as a potential hepatocellular carcinoma (HCC) diagnostic and/or therapeutic target. GPC3 has been found to be up-regulated in HCC and to be absent in normal and cirrhotic liver. As yet, however, the molecular characteristics of GPC3 and its role in HCC cell physiology and development are still undefined. METHODS: Human hepatocyte cultures were established from 10 HCC patients. Additional liver samples were obtained from 5 patients without cirrhosis and/or HCC...
December 4, 2017: Cellular Oncology (Dordrecht)
Zhen Wang, Yan-Jiang Han, Shun Huang, Meng Wang, Wen-Lan Zhou, Hong-Sheng Li, Quan-Shi Wang, Hu-Bing Wu
The glypican-3 (GPC3) receptor is overexpressed in hepatocellular carcinoma (HCC) and is a potential diagnostic and therapeutic target. GPC3-targeted molecular imaging will be helpful to differentiate diagnosis and guide therapy. In the present study, we will develop a novel PET probe for imaging the expression of GPC-3. L5 (sequence: RLNVGGTYFLTTRQ), a GPC3 targeting peptide, was labeled with 5-carboxyfluorescein (FAM) and18 F-fluoride. Cell binding tests were performed to identify the binding specificity of FAM-L5 and18 F radiolabeled peptide...
February 2018: Amino Acids
Jiang-Zheng Zeng, Yu Liu, Fen Huang, Zhi-Hui He, Huamao Sun, Yan-Da Lu, Jun-Hua Lei, Rong-Cheng Luo
OBJECTIVE: To investigate potential human leucocyte antigen (HLA)-A2-restricted epitope peptides of glypican-3 (GPC3) and determine the cytotoxicity of peptide-specific cytotoxic T lymphocytes (CTLs) against hepatocellular carcinoma (HCC) cells. METHODS: The potential HLA-A*0201-restricted GPC3 peptides were screened using computer algorithms, T2 cell-binding affinity and stability of peptide/HLA-A*0201 complex assay. The peptide-specific CTLs were generated and their cytotoxicity against GPC3+ SMMC 7721 and HepG2 cells was detected using IFN-γ based enzyme-linked immunospot and lactate dehydrogenase release assays in vitro...
November 2017: Asian Pacific Journal of Tropical Medicine
Qing-Bo Zhao, Rong-Rong Liao, Hao Sun, Zhe Zhang, Qi-Shan Wang, Chang-Suo Yang, Xiang-Zhe Zhang, Yu-Chun Pan
The Dongxiang Blue-shelled chicken is one of the most valuable Chinese indigenous poultry breeds. However, compared to the Italian native White Leghorn, although this Chinese breed possesses numerous favorable characteristics, it also exhibits lower growth performance and fertility. Here, we utilized genotyping sequencing data obtained via genome reduction on a sequencing platform to detect 100,114 single nucleotide polymorphisms and perform further biological analysis and functional annotation. We employed cross-population extended haplotype homozygosity, eigenvector decomposition combined with genome-wide association studies (EigenGWAS), and efficient mixed-model association expedited methods to detect areas of the genome that are potential selected regions (PSR) in both chicken breeds, and performed gene ontology (GO) enrichment and quantitative trait loci (QTL) analyses annotating using the Kyoto Encyclopedia of Genes and Genomes...
February 2, 2018: G3: Genes—Genomes—Genetics
Stanislav Naryzhny, Victor Zgoda, Artur Kopylov, Elena Petrenko, Olga Kleist, Аlexander Archakov
We have previously developed an approach, where two-dimensional gel electrophoresis (2DE) was used, followed by sectional analysis of the whole gel using high-resolution nano-liquid chromatography-mass spectrometry (ESI LC-MS/MS). In this study, we applied this approach on the panoramic analysis of proteins and their proteoforms from normal (liver) and cancer (HepG2) cells. This allowed us to detect, in a single proteome, about 20,000 proteoforms coded by more than 4000 genes. A set of 3D-graphs showing distribution of these proteoforms in 2DE maps (profiles) was generated...
November 23, 2017: Proteomes
Nobuhiro Tsuchiya, Toshiaki Yoshikawa, Norihiro Fujinami, Keigo Saito, Shoichi Mizuno, Yu Sawada, Itaru Endo, Tetsuya Nakatsura
We have previously conducted a phase I trial to test the efficacy of a glypican-3 (GPC3) peptide vaccine in patients with advanced hepatocellular carcinoma (HCC); however, its immunological mechanism of action remains unclear. Here, we report a pilot study conducted to evaluate the immunological mechanisms of action of this GPC3 peptide vaccine (UMIN-CTR number 000005093). Eleven patients with advanced HCC were vaccinated with the GPC3 peptide in this trial. The primary end point was GPC3 peptide-specific immune response induced by the GPC3 peptide vaccination...
2017: Oncoimmunology
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