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https://www.readbyqxmd.com/read/29345911/role-of-glycanation-and-convertase-maturation-of-the-soluble-glypican-3-in-inhibiting-proliferation-of-hepatocellular-carcinoma-cells
#1
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
https://www.readbyqxmd.com/read/29339014/development-of-gpc3-specific-chimeric-antigen-receptor-engineered-natural-killer-cells-for-the-treatment-of-hepatocellular-carcinoma
#2
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
https://www.readbyqxmd.com/read/29259231/a-novel-cell-line-based-orthotopic-xenograft-mouse-model-that-recapitulates-human-hepatoblastoma
#3
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
https://www.readbyqxmd.com/read/29240237/non-isolated-diaphragmatic-hernia-in-simpson-golabi-behmel-syndrome
#4
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
https://www.readbyqxmd.com/read/29226636/the-value-of-gpc3-and-gp73-in-clinical-diagnosis-of-hepatocellular-carcinoma
#5
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
https://www.readbyqxmd.com/read/29204978/role-of-glypican-3-in-the-growth-migration-and-invasion-of-primary-hepatocytes-isolated-from-patients-with-hepatocellular-carcinoma
#6
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)
https://www.readbyqxmd.com/read/29204748/imaging-the-expression-of-glypican-3-in-hepatocellular-carcinoma-by-pet
#7
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) and 18F-fluoride. Cell binding tests were performed to identify the binding specificity of FAM-L5 and 18F radiolabeled peptide...
December 4, 2017: Amino Acids
https://www.readbyqxmd.com/read/29203107/glypican-3-specific-cytotoxic-t-lymphocytes-induced-by-human-leucocyte-antigen-a-0201-restricted-peptide-effectively-kill-hepatocellular-carcinoma-cells-in%C3%A2-vitro
#8
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
https://www.readbyqxmd.com/read/29187421/identifying-genetic-differences-between-dongxiang-blue-shelled-and-white-leghorn-chickens-using-sequencing-data
#9
Qingbo 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. We utilize genotyping sequencing data in this paper obtained via genome reduction on a sequencing platform to detect 100,114 single nucleotide polymorphisms (SNPs) and perform further biological analysis and functional annotation...
November 29, 2017: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/29168748/variety-and-dynamics-of-proteoforms-in-the-human-proteome-aspects-of-markers-for-hepatocellular-carcinoma
#10
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
https://www.readbyqxmd.com/read/29123959/immunological-efficacy-of-glypican-3-peptide-vaccine-in-patients-with-advanced-hepatocellular-carcinoma
#11
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
https://www.readbyqxmd.com/read/29113314/glypican-3-induces-oncogenicity-by-preventing-igf-1r-degradation-a-process-that-can-be-blocked-by-grb10
#12
Wei Cheng, Po-Chun Huang, Hsiao-Mei Chao, Yung-Ming Jeng, Hey-Chi Hsu, Hung-Wei Pan, Wuh-Liang Hwu, Yu-May Lee
Hepatocellular carcinoma (HCC) is the most common primary liver malignancy and is a major cause of cancer-related death worldwide. Previously, we demonstrated that glypican-3 (GPC3) is highly expressed in HCC, and that GPC3 induces oncogenicity and promotes the growth of cancer cells through IGF-1 receptor (IGF-1R). In the present study, we investigated the mechanisms of GPC3-mediated enhancement of IGF-1R signaling. We demonstrated that GPC3 decreased IGF-1-induced IGF-1R ubiquitination and degradation and increased c-Myc protein levels...
October 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/29106433/codelivery-of-sorafenib-and-gpc3-sirna-with-pei-modified-liposomes-for-hepatoma-therapy
#13
Weitong Sun, Yong Wang, Mingyue Cai, Liteng Lin, Xiaoyan Chen, Zhong Cao, Kangshun Zhu, Xintao Shuai
Hepatocellular carcinoma (HCC) is one of the most common malignancies imposing a serious threat to human health worldwide. To date, the effect of HCC chemotherapy has been limited due to drug resistance. Combination therapy of chemotherapeutic drugs and siRNA represents an emerging strategy that may improve anticancer effects by synergistic actions. The current study was aimed at achieving better HCC treatment via combination therapy, in which PEI-modified liposomes prepared by a thin-film hydration method were used to codeliver sorafenib (SF) and siRNA targeting GPC3 gene (siGPC3)...
November 6, 2017: Biomaterials Science
https://www.readbyqxmd.com/read/29025594/gene-expression-profiling-pathway-analysis-and-subtype-classification-reveal-molecular-heterogeneity-in-hepatocellular-carcinoma-and-suggest-subtype-specific-therapeutic-targets
#14
Rahul Agarwal, Jitendra Narayan, Amitava Bhattacharyya, Mayank Saraswat, Anil Kumar Tomar
A very low 5-year survival rate among hepatocellular carcinoma (HCC) patients is mainly due to lack of early stage diagnosis, distant metastasis and high risk of postoperative recurrence. Hence ascertaining novel biomarkers for early diagnosis and patient specific therapeutics is crucial and urgent. Here, we have performed a comprehensive analysis of the expression data of 423 HCC patients (373 tumors and 50 controls) downloaded from The Cancer Genome Atlas (TCGA) followed by pathway enrichment by gene ontology annotations, subtype classification and overall survival analysis...
October 2017: Cancer Genetics
https://www.readbyqxmd.com/read/28987030/identifying-hipk1-as-target-of-mir-22-3p-enhancing-recombinant-protein-production-from-hek-293-cell-by-using-microarray-and-htp-sirna-screen
#15
Sarah Inwood, Eugen Buehler, Michael Betenbaugh, Madhu Lal, Joseph Shiloach
Protein expression from human embryonic kidney cells (HEK 293) is an important tool for structural and clinical studies. It is previously shown that microRNAs (small, noncoding RNAs) are effective means for improved protein expression from these cells, and by conducting a high-throughput screening of the human microRNA library, several microRNAs are identified as potential candidates for improving expression. From these, miR-22-3p is chosen for further study since it increased the expression of luciferase, two membrane proteins and a secreted fusion protein with minimal effect on the cells' growth and viability...
October 7, 2017: Biotechnology Journal
https://www.readbyqxmd.com/read/28978751/an-anti-glypican-3-cd3-bispecific-t-cell-redirecting-antibody-for-treatment-of-solid-tumors
#16
Takahiro Ishiguro, Yuji Sano, Shun-Ichiro Komatsu, Mika Kamata-Sakurai, Akihisa Kaneko, Yasuko Kinoshita, Hirotake Shiraiwa, Yumiko Azuma, Toshiaki Tsunenari, Yoko Kayukawa, Yukiko Sonobe, Natsuki Ono, Kiyoaki Sakata, Toshihiko Fujii, Yoko Miyazaki, Mizuho Noguchi, Mika Endo, Asako Harada, Werner Frings, Etsuko Fujii, Eitaro Nanba, Atsushi Narita, Akihisa Sakamoto, Tetsuya Wakabayashi, Hiroko Konishi, Hiroaki Segawa, Tomoyuki Igawa, Takashi Tsushima, Hironori Mutoh, Yukari Nishito, Mina Takahashi, Lorraine Stewart, Ehab ElGabry, Yoshiki Kawabe, Masaki Ishigai, Shuichi Chiba, Masahiro Aoki, Kunihiro Hattori, Junichi Nezu
Cancer care is being revolutionized by immunotherapies such as immune checkpoint inhibitors, engineered T cell transfer, and cell vaccines. The bispecific T cell-redirecting antibody (TRAB) is one such promising immunotherapy, which can redirect T cells to tumor cells by engaging CD3 on a T cell and an antigen on a tumor cell. Because T cells can be redirected to tumor cells regardless of the specificity of T cell receptors, TRAB is considered efficacious for less immunogenic tumors lacking enough neoantigens...
October 4, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28978053/heparin-antagonizes-cisplatin-resistance-of-a2780-ovarian-cancer-cells-by-affecting-the-wnt-signaling-pathway
#17
Daniel Bastian Pfankuchen, Fabian Baltes, Tahira Batool, Jin-Ping Li, Martin Schlesinger, Gerd Bendas
Low molecular weight heparin (LMWH), the guideline based drug for prophylaxis and treatment of cancer-associated thrombosis, was recently shown to sensitize cisplatin resistant A2780cis human ovarian cancer cells for cisplatin cytotoxicity upon 24 h pretreatment with 50 μg × mL(-1) of the LMWH tinzaparin in vitro, equivalent to a therapeutic dosage. Thereby, LMWH induced sensitization by transcriptional reprogramming of A2780cis cells via not yet elucidated mechanisms that depend on cellular proteoglycans...
September 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28970139/fetal-gut-like-differentiation-in-gallbladder-cancer
#18
Kei Koyama, Daichi Maeda, Daisuke Tamura, Chisato Narita, Yukitsugu Kudo-Asabe, Tsutomu Sato, Yuzo Yamamoto, Masato Sageshima, Hiroshi Nanjo, Akiteru Goto
Adenocarcinomas showing fetal gut-like (enteroblastic) differentiation can arise in a variety of organs, and are frequently accompanied by an elevated serum alpha-fetoprotein (AFP) level. However, no study has investigated fetal gut-like differentiation in gallbladder cancer in detail. Herein, we performed morphological and immunohistochemical analyses of fetal-gut like differentiation in 49 consecutive gallbladder cancer cases. The expression of Sal-like protein 4 (SALL4), an embryonic stem cell marker reported to represent fetal gut-like differentiation, as well as other oncofetal proteins, including glypican-3 (GPC3) and AFP, were assessed...
September 29, 2017: Human Pathology
https://www.readbyqxmd.com/read/28881778/treatment-of-hepatocellular-carcinoma-with-a-gpc3-targeted-bispecific-t-cell-engager
#19
Yanyu Bi, Hua Jiang, Peng Wang, Bo Song, Huamao Wang, Xianming Kong, Zonghai Li
There are limited strategies for the treatment of hepatocellular carcinoma (HCC). In this study, we prepared a Bispecific T cell engager (BiTE) targeting Glypican 3 (GPC3) and CD3. The GPC3/CD3 BiTE was prepared by fusing the single-chain variable fragment (scFv) of the humanized anti-GPC3 antibody (9F2) with the scFv of the anti-CD3 antibody (OKT3). The in vitro and in vivo cytotoxic activities of the GPC3/CD3 BiTE were evaluated against various HCC cell lines. The GPC3/CD3 BiTE could efficiently mediate the T cell killing of GPC3-positive HCC in vitro, which was dependent on GPC3 expression on the surface of HCC cells...
August 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28881044/from-large-to-small-the-immunohistochemical-panel-in-the-diagnosis-of-early-hepatocellular-carcinoma
#20
Francesco Vasuri, Deborah Malvi, Sonia Bonora, Silvia Fittipaldi, Matteo Renzulli, Francesco Tovoli, Rita Golfieri, Luigi Bolondi, Antonia D'Errico
AIMS: The aims of this study were to: validate the use of the immunohistochemical (IHC) markers glutamine synthetase (GS), glypican-3 (GPC3), heat shock protein-70 (HSP70) and enhancer of zeste homologue 2 (EZH2) in liver biopsies for the differential diagnosis between small hepatocellular carcinoma (HCC) and non-neoplastic liver nodules, with special attention to <10-mm nodules; and assess the actual sensitivity and specificity of the single markers, and their combination, in needle biopsies...
September 7, 2017: Histopathology
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