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https://www.readbyqxmd.com/read/27878117/gpc-3-in-hepatocellular-carcinoma-current-perspectives
#1
REVIEW
Yongle Wu, Hui Liu, Huiguo Ding
Glypican-3 (GPC3), a member of heparan sulfate proteoglycans, attaches to the cell membrane and is frequently observed to be elevated in hepatocellular carcinoma (HCC). However, GPC3 is not detected in normal liver tissues and benign liver lesions. Consequently, GPC3 is currently being used as a diagnostic biomarker and HCC-specific positron emission computed tomography probe to identify HCCs in normal liver tissues and benign liver lesions. The overexpression of GPC-3 in serum or liver tissue also predicts poor prognosis for HCC patients...
2016: Journal of Hepatocellular Carcinoma
https://www.readbyqxmd.com/read/27862961/identification-of-a-glypican-3-binding-peptide-for-in-vivo-non-invasive-human-hepatocellular-carcinoma-detection
#2
Zainen Qin, Jingjing Wang, Ye Wang, Guohao Wang, Xiangyu Wang, Zhiyang Zhou, Gang Liu, Shi Gao, Lei Zhu
Early and accurate detection of hepatocellular carcinoma (HCC) is essential to improve the prognosis of patients and reduce the morbidity of surgical therapy. Glypican-3 (GPC3) is a protein abnormally expressed in HCC that has been identified as a serological and histochemical HCC marker. A novel peptide that specifically recognizes GPC3 will facilitate early detection of HCC and guide the treatment strategy. Herein, phage display screening technology is utilized to obtain a GPC3 binding peptide (GBP) using HCC cells expressing GPC3 in varying abundances...
November 15, 2016: Macromolecular Bioscience
https://www.readbyqxmd.com/read/27790374/loss-of-function-mutations-and-global-rearrangements-in-gpc3-in-patients-with-simpson-golabi-behmel-syndrome
#3
Keiko Shimojima, Yumiko Ondo, Eriko Nishi, Seiji Mizuno, Miharu Ito, Aya Ioi, Mariko Shimizu, Maho Sato, Masami Inoue, Nobuhiko Okamoto, Toshiyuki Yamamoto
Simpson-Golabi-Behmel syndrome is a congenital malformation syndrome associated with mutations in GPC3, which is located in the Xq26 region. Three new loss-of-function mutations and a global X-chromosome rearrangement involving GPC3 were identified. A female sibling of the patient, who presented with a cleft palate and hepatoblastoma, carries the same chromosomal rearrangement and a paradoxical pattern of X-chromosome inactivation. These findings support variable GPC3 alterations, with a possible mechanism in female patients...
2016: Human Genome Variation
https://www.readbyqxmd.com/read/27758865/an-unbiased-mass-spectrometry-approach-identifies-glypican-3-as-an-interactor-of-proprotein-convertase-subtilisin-kexin-type-9-pcsk9-and-low-density-lipoprotein-receptor-ldlr-in-hepatocellular-carcinoma-cells
#4
Kévin Ly, Rachid Essalmani, Roxane Desjardins, Nabil G Seidah, Robert Day
The mechanism of LDL receptor (LDLR) degradation mediated by the proprotein convertase subtilisin/kexin type 9 (PCSK9) has been extensively studied; however, many steps within this process remain unclear and still require characterization. Recent studies have shown that PCSK9 lacking its Cys/His-rich domain can still promote LDLR internalization, but the complex does not reach the lysosome suggesting the presence of an additional interaction partner(s). In this study we carried out an unbiased screening approach to identify PCSK9-interacting proteins in the HepG2 cells' secretome using co-immunoprecipitation combined with mass spectrometry analyses...
November 18, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27739211/simpson-golabi-behmel-syndrome-in-a-female-a-case-report-and-an-unsolved-issue
#5
Alessandro Vaisfeld, Maria Grazia Pomponi, Roberta Pietrobono, Elisabetta Tabolacci, Giovanni Neri
Simpson-Golabi-Behmel syndrome is an X-linked recessive overgrowth condition caused by alterations in GPC3 gene, encoding for the cell surface receptor glypican 3, whose clinical manifestations in affected males are well known. Conversely, there is little information regarding affected females, with very few reported cases, and a clinical definition of this phenotype is still lacking. In the present report we describe an additional case, the first to receive a primary molecular diagnosis based on strong clinical suspicion...
October 14, 2016: American Journal of Medical Genetics. Part A
https://www.readbyqxmd.com/read/27729630/glypican-3-level-assessed-by-the-enzyme-linked-immunosorbent-assay-is-inferior-to-alpha-fetoprotein-level-for-hepatocellular-carcinoma-diagnosis
#6
Yejoo Jeon, Eun Sun Jang, Yun Suk Choi, Jin-Wook Kim, Sook-Hyang Jeong
BACKGROUND/AIMS: Glypican-3 (GPC3) protein is highly expressed in hepatocellular carcinoma (HCC) tissue. It has been suggested as a diagnostic biomarker, but its inconsistent performance means that it requires further assessment. We therefore investigated the diagnostic value of the plasma GPC3 level compared to the alpha-fetoprotein (AFP) level as a diagnostic biomarker of HCC. METHODS: We enrolled 157 consecutive patients with newly diagnosed HCC and 156 patients with liver cirrhosis (LC) as the control group...
September 2016: Clinical and Molecular Hepatology
https://www.readbyqxmd.com/read/27716032/expressed-alleles-of-imprinted-igf2-dlk1-and-meg3-colocalize-in-3d-preserved-nuclei-of-porcine-fetal-cells
#7
Yvette Lahbib-Mansais, Harmonie Barasc, Maria Marti-Marimon, Florence Mompart, Eddie Iannuccelli, David Robelin, Juliette Riquet, Martine Yerle-Bouissou
BACKGROUND: To explore the relationship between spatial genome organization and gene expression in the interphase nucleus, we used a genomic imprinting model, which offers parental-specific gene expression. Using 3D FISH in porcine fetal liver cells, we compared the nuclear organization of the two parental alleles (expressed or not) of insulin-like growth factor 2 (IGF2), a paternally imprinted gene located on chromosome 2. We investigated whether its nuclear positioning favors specific locus associations...
October 1, 2016: BMC Cell Biology
https://www.readbyqxmd.com/read/27692382/peroxidase-like-catalytic-activity-of-copper-ions-and-its-application-for-highly-sensitive-detection-of-glypican-3
#8
Aixian Zheng, Xiaolong Zhang, Ju Gao, Xiaolong Liu, Jingfeng Liu
Glypican-3 (GPC3) might be used as new biomarker of liver cancer for the development of new diagnostic methods. The most commonly used methods for protein detection are based on natural enzymes, which are easily affected by environmental conditions and suffer from the rigorous preparation conditions. Thus, the development of new enzyme mimetics with high and stable catalytic activity is of great significance in diagnostic applications. In this paper, copper ions (Cu(2+)) was found to possess the peroxidase-like catalytic activity, which can catalyze H2O2-mediated oxidation of peroxidase substrate and obtain the oxidation product with color change...
October 19, 2016: Analytica Chimica Acta
https://www.readbyqxmd.com/read/27689616/glypican-3-and-krt19-are-markers-associating-with-metastasis-and-poor-prognosis-of-pancreatic-ductal-adenocarcinoma
#9
Hongliang Yao, Zhulin Yang, Ziru Liu, Xiongying Miao, Leping Yang, Daiqiang Li, Qiong Zou, Yuan Yuan
OBJECTIVE: Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant tumor with metastasis in most patients at diagnosis. The molecular mechanisms associated with its high malignancy have not been fully elucidated. This study investigated the clinicopathological significances of GPC3 and KRT19 expression in PDAC. METHODS: GPC3, KRT19, and CA19-9 protein expression were measured by immunohistochemistry. RESULTS: GPC3 and KRT19 protein levels were overexpressed in PDAC tumors compared to normal pancreatic tissues, benign pancreatic tissues, and peritumoral tissues (P< 0...
September 22, 2016: Cancer Biomarkers: Section A of Disease Markers
https://www.readbyqxmd.com/read/27669301/glypican-3-targeting-immunotoxins-for-the-treatment-of-liver-cancer
#10
REVIEW
Bryan D Fleming, Mitchell Ho
Hepatocellular carcinoma (HCC) is the most common form of primary liver cancer, yet no effective therapeutics exist. This review provides an overview of the recent development of recombinant immunotoxins for the treatment of glypican-3 (GPC3) expressing HCC. GPC3 is a cell surface heparan sulfate proteoglycan that is overexpressed in HCC, but is absent from normal adult human tissues. Treatment of HCC with anti-GPC3 immunotoxins represents a new therapeutic option. Using phage display and hybridoma technologies, three high affinity antibodies (HN3, HS20 and YP7) have been generated against GPC3...
September 22, 2016: Toxins
https://www.readbyqxmd.com/read/27667400/humanization-of-high-affinity-antibodies-targeting-glypican-3-in-hepatocellular-carcinoma
#11
Yi-Fan Zhang, Mitchell Ho
Glypican-3 (GPC3) is a cell-surface heparan sulfate proteoglycan highly expressed in hepatocellular carcinoma (HCC). We have generated a group of high-affinity mouse monoclonal antibodies targeting GPC3. Here, we report the humanization and testing of these antibodies for clinical development. We compared the affinity and cytotoxicity of recombinant immunotoxins containing mouse single-chain variable regions fused with a Pseudomonas toxin. To humanize the mouse Fvs, we grafted the combined KABAT/IMGT complementarity determining regions (CDR) into a human IgG germline framework...
September 26, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27650540/bone-morphogenetic-protein-9-is-a-potent-growth-inhibitor-of-hepatocellular-carcinoma-and-reduces-the-liver-cancer-stem-cells-population
#12
Jae Woo Jung, So-Mi Yoon, Subin Kim, Yun-Hui Jeon, Byung-Hak Yoon, Su-Geun Yang, Min Kyoung Kim, Senyon Choe, Mario Meng-Chiang Kuo
The biological role of BMP-9 signaling in liver cancer remains dubious. To explore the potential use of BMP-9 signaling for anti-cancer therapy, we used recombinant human BMP-9, which we referred to as MB109, to study the effect on growth of fifteen hepatocellular carcinoma (HCC) cell lines. MB109 effectively inhibits the proliferation of nine HCC cells in vitro. The anti-proliferative effect was found to be induced by turning on p21 signaling, which caused survivin suppression and G0/G1 cell cycle arrest. ID3 was identified to be the mediator of the MB109-induced p21 expression...
September 16, 2016: Oncotarget
https://www.readbyqxmd.com/read/27633306/effect-of-co-transfection-of-mir-520c-3p-and-mir-132-on-proliferation-and-apoptosis-of-hepatocellular-carcinoma-huh7
#13
Chang-Jiang Lei, Chun Yao, De-Ke Li, Zhi-Xiong Long, Yuan Li, Dan Tao, Yan-Ping Liou, Jiang-Zhou Zhang, Ning Liu
OBJECTIVE: To investigate the effects of co-transfection of miR-520c-3p and miR-132 on proliferation and apoptosis of hepatocellular carcinoma Huh7. METHODS: Hepatocellular carcinoma Huh7 was cultured in vitro and lipidosome was used to transfect miR-520c-3p and miR-132, respectively or together. The effects of transfection of miR-520c-3p and miR-132 on proliferation and apoptosis of Huh7 were detected by CCK8 and Annexin V staining and flow cytometry, and the expression level of the targeted gene of over-expressed miR-520c-3p and miR-132 was determined by Western blot and realtime PCR...
September 2016: Asian Pacific Journal of Tropical Medicine
https://www.readbyqxmd.com/read/27612164/prenatal-diagnosis-of-simpson-golabi-behmel-syndrome
#14
Pamela Magini, Flavia Palombo, Simona Boito, Giulia Lanzoni, Patrizia Mongelli, Tommaso Rizzuti, Marco Baccarin, Tommaso Pippucci, Marco Seri, Faustina Lalatta
Simpson-Golabi-Behmel syndrome (SGBS) is an overgrowth syndrome and it is usually diagnosed postnatally, on the basis of phenotype. Prenatal ultrasonography may show fetal alterations, but they are not pathognomonic and most of them are frequently detectable only from the 20th week of gestation. Nevertheless, early diagnosis is important to avoid neonatal complications and make timely and informed decisions about the pregnancy. We report on four fetuses from two unrelated families, in whom the application of whole exome sequencing and array-CGH allowed the identification of GPC3 alterations causing SGBS...
September 9, 2016: American Journal of Medical Genetics. Part A
https://www.readbyqxmd.com/read/27601357/aptamers-against-cells-overexpressing-glypican%C3%A2-3-from-expanded-genetic-systems-combined-with-cell-engineering-and-laboratory-evolution
#15
Liqin Zhang, Zunyi Yang, Thu Le Trinh, I-Ting Teng, Sai Wang, Kevin M Bradley, Shuichi Hoshika, Qunfeng Wu, Sena Cansiz, Diane J Rowold, Christopher McLendon, Myong-Sang Kim, Yuan Wu, Cheng Cui, Yuan Liu, Weijia Hou, Kimberly Stewart, Shuo Wan, Chen Liu, Steven A Benner, Weihong Tan
Laboratory in vitro evolution (LIVE) might deliver DNA aptamers that bind proteins expressed on the surface of cells. In this work, we used cell engineering to place glypican 3 (GPC3), a possible marker for liver cancer theranostics, on the surface of a liver cell line. Libraries were then built from a six-letter genetic alphabet containing the standard nucleobases and two added nucleobases (2-amino-8H-imidazo[1,2-a][1,3,5]triazin-4-one and 6-amino-5-nitropyridin-2-one), Watson-Crick complements from an artificially expanded genetic information system (AEGIS)...
September 26, 2016: Angewandte Chemie
https://www.readbyqxmd.com/read/27589329/whole-exome-sequencing-and-array-based-molecular-karyotyping-as-aids-to-prenatal-diagnosis-in-fetuses-with-suspected-simpson-golabi-behmel-syndrome
#16
Christina Kehrer, Alexander Hoischen, Ralf Menkhaus, Eva Schwab, Andreas Müller, Sarah Kim, Martina Kreiß, Valerie Weitensteiner, Alina Hilger, Christoph Berg, Anne Geipel, Heiko Reutter, Ulrich Gembruch
OBJECTIVE: Simpson-Golabi-Behmel (SGBS) syndrome type 1 and type 2 represent rare X-linked prenatal overgrowth disorders. The aim of our study is to describe the prenatal sonographic features as well as the genetic work-up. METHOD: Retrospective analysis of four cases with a pre- or postnatal diagnosis of SGBS in a single tertiary referral center within a period of 4 years. RESULTS: In the study period, four male fetuses with SGBS were detected...
October 2016: Prenatal Diagnosis
https://www.readbyqxmd.com/read/27573079/long-noncoding-rna-glypican-3-gpc3-antisense-transcript-1-promotes-hepatocellular-carcinoma-progression-via-epigenetically-activating-gpc3
#17
Xiao-Ting Zhu, Ji-Hang Yuan, Teng-Teng Zhu, Yang-Yang Li, Xiao-Yang Cheng
Long noncoding RNA (lncRNA) have critical roles in various pathophysiological processes, and are frequently dysregulated in many diseases, particularly in cancer. The lncRNA glypican 3 antisense transcript 1 (GPC3-AS1) has been reported to be a potential biomarker for hepatocellular carcinoma (HCC) screening. However, the exact biological functions of GPC3-AS1 in HCC, and its roles and regulation mechanisms regarding GPC3 are still unknown. In this study, we observed a significant upregulation of GPC3-AS1 in HCC...
October 2016: FEBS Journal
https://www.readbyqxmd.com/read/27563447/a-genetic-database-can-be-utilized-to-identify-potential-biomarkers-for-biphenotypic-hepatocellular-carcinoma-cholangiocarcinoma
#18
Shaffer R S Mok, Sachin Mohan, Navjot Grewal, Adam B Elfant, Thomas A Judge
BACKGROUND: Biphenotypic hepatocellular carcinoma-cholangiocarcinoma (HCC-CC) is an uncommon primary liver neoplasm. Due to limitations in radiologic imaging for the diagnosis of this condition, biopsy is a common method for diagnosis, which is invasive and holds potential complications. To identify alternative means for obtaining the diagnosis and assessing the prognosis of this condition, we evaluated biomarkers for biphenotypic HCC-CC using a genetic database. METHODS: To evaluate the genetic associations with each variable we utilized GeneCards(®), The Human Gene Compendium (http://www...
August 2016: Journal of Gastrointestinal Oncology
https://www.readbyqxmd.com/read/27552844/combined-hepatocellular-and-cholangiocarcinoma-originating-from-the-same-clone-a-pathomolecular-evidence-based-study
#19
Qian Zhao, Wen-Long Yu, Xin-Yuan Lu, Hui Dong, Yi-Jin Gu, Xia Sheng, Wen-Ming Cong, Meng-Chao Wu
BACKGROUND: Combined hepatocellular and cholangiocarcinoma (CHC) is a unique subtype of liver cancer comprising both hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC); however, its cellular origin remains unclear. The purpose of this study was to investigate the clinicopathologic features and the clonal relationship between HCC and ICC in 34 patients with CHC. METHODS: The clinicopathologic features and prognosis of the 34 CHC patients were compared with those of 29 patients with separated HCC and ICC (SHC)...
2016: Chinese Journal of Cancer
https://www.readbyqxmd.com/read/27530312/redirecting-t-cells-to-glypican-3-with-4-1bb-zeta-chimeric-antigen-receptors-results-in-th1-polarization-and-potent-antitumor-activity
#20
Wenpeng Li, Linjie Guo, Purva Rathi, Ekaterina Marinova, Xiuhua Gao, Meng-Feng Wu, Hao Liu, Gianpietro Dotti, Stephen Gottschalk, Leonid S Metelitsa, Andras Heczey
T cells engineered to express CD19-specific chimeric antigen receptors (CARs) have shown breakthrough clinical successes in patients with B-cell lymphoid malignancies. However, similar therapeutic efficacy of CAR T cells in solid tumors is yet to be achieved. In this study we systematically evaluated a series of CAR constructs targeting glypican-3 (GPC3), which is selectively expressed on several solid tumors. We compared GPC3-specific CARs that encoded CD3ζ (Gz) alone or with costimulatory domains derived from CD28 (G28z), 4-1BB (GBBz), or CD28 and 4-1BB (G28BBz)...
August 16, 2016: Human Gene Therapy
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