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https://www.readbyqxmd.com/read/28276470/simple-risk-score-for-prediction-of-early-recurrence-of-hepatocellular-carcinoma-within-the-milan-criteria-after-orthotopic-liver-transplantation
#1
Jiliang Feng, Jushan Wu, Ruidong Zhu, Dezhao Feng, Lu Yu, Yan Zhang, Dayu Bu, Chenlei Li, Yuyan Zhou, Lianghao Si, Yuhan Liu, Ziwei Liang, Jianing Xu, Tianjun Wu
Ten to twenty percent of the hepatocellular carcinoma (HCC) patients fulfilling the Milan criteria (MC) recurred within three years after orthotopic liver transplantation (OLT). We therefore utilize a training cohort to develop an improved prognostic model for predicting the recurrence in these patients. By univariate and multivariate analysis, AFP level [cut-off value: 321 ng/mL, area under the curve (AUC) = 0.724, 95% confidence interval (CI) = 0.604-0.843, P < 0.001] and cytokeratin-19 (CK19) and glypican-3 (GPC3) expression pattern from nine putative prognostic factors were entered in risk factor scoring model to conjecture the tumor recurrence...
March 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28207681/significance-of-glypican-3-gpc3-expression-in-hepatocellular-cancer-diagnosis
#2
Bin Sun, Zhi Huang, Bi Wang, Yanglong Yu, Shihai Lin, Lei Luo, Yuzhu Wang, Zheng Huang
BACKGROUND Primary hepatocellular carcinoma (HCC) is a malignant tumor that is common China. Early diagnosis is of great significance for improving treatment efficiency. GPC3 level is closely related to HCC occurrence. This study investigated GPC3 expression in HCC patient serum and tissue, and assessed the significance of GPC3 combined AFP detection in HCC diagnosis. MATERIAL AND METHODS A total of 76 HCC patients in our hospital were enrolled. Immunohistochemistry was applied to test GPC3 expression in cancer tissue and para-carcinoma tissue...
February 16, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28198497/nested-polymerase-chain-reaction-technique-for-the-detection-of-gpc3-and-afp-mrna-in-liver-cancer-micrometastases
#3
J Luo, K Yang, Y G Wen
The incidence of liver cancer has gradually risen to a high level in China, and tumor metastasis occurs via multiple pathways. Alpha fetal protein (AFP) is the main biomarker of liver cancer micrometastases. A recent study showed that glypican-3 (GPC3), which is abundant in hepatoma cells, has promising specificity and could be used to determine the presence of malignant cells. The nested polymerase chain reaction (PCR) technique is superior in experimental sensitivity. Using rat models of liver cancer in the current study, we utilized nested PCR to detect Gpc3 and Afp mRNA to determine their relationship with liver cancer micrometastases...
February 8, 2017: Genetics and Molecular Research: GMR
https://www.readbyqxmd.com/read/28120036/phase-ib-study-of-codrituzumab-in-combination-with-sorafenib-in-patients-with-non-curable-advanced-hepatocellular-carcinoma-hcc
#4
Ghassan K Abou-Alfa, Chia-Jui Yen, Chih-Hung Hsu, Joseph O'Donoghue, Volkan Beylergil, Shutian Ruan, Neeta Pandit-Taskar, Bolorsukh Gansukh, Serge K Lyashchenko, Jennifer Ma, Peter Wan, Yu-Yun Shao, Zhong-Zhe Lin, Catherine Frenette, Bert O'Neil, Lawrence Schwartz, Peter M Smith-Jones, Toshihiko Ohtomo, Takayoshi Tanaka, Hideo Morikawa, Yuko Maki, Norihisa Ohishi, Ya-Chi Chen, Tamara Agajanov, Frederic Boisserie, Laura Di Laurenzio, Ray Lee, Steven M Larson, Ann-Lii Cheng, Jorge A Carrasquilo
PURPOSE: Codrituzumab, a humanized antibody against glypican-3, is highly expressed in HCC. A phase I study evaluated the combination with sorafenib in HCC. PATIENTS AND METHODS: In a 3 + 3 design, codrituzumab was given intravenously in various doses with sorafenib 400 mg twice daily to patients with advanced HCC, age ≥18, ECOG 0-1, Child-Pugh A and B7, adequate organ functions, and no prior systemic therapy, with tumor assessment by RECIST 1.0 and safety by CTCAE 3...
February 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28087980/the-significance-of-glypican-3-expression-profiling-in-the-tumor-cellular-origin-theoretical-system-for-hepatocellular-carcinoma-progression
#5
Ran Xue, Jiliang Feng, Qinghua Meng, Fudong Lv, Yueke Zhu, Hongwei Yu, Shijie Zhang, Chenzhao Song, Lin Sun, Zhujun Yue, Shuai Feng, Ruiwen Che, Qian Xiang, Xiaodan Jing
AIMS: Glypican-3(GPC3) expression is correlated with poor prognosis and progression in hepatocellular carcinoma (HCC). HCC progression can be associated with the differentiation status of tumor cell before malignant transformation. Our aim was to investigate the dynamic expression of GPC3 during tumor cells differentiation and to explore the role and theoretical significance of GPC3 in malignant essence of HCC. METHODS: The expressions of tissue GPC3 and alpha-fetoprotein (AFP) were detected by immunohistochemical staining...
January 14, 2017: Journal of Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28035433/development-of-t-cells-carrying-two-complementary-chimeric-antigen-receptors-against-glypican-3-and-asialoglycoprotein-receptor-1-for-the-treatment-of-hepatocellular-carcinoma
#6
Cheng Chen, Kesang Li, Hua Jiang, Fei Song, Huiping Gao, Xiaorong Pan, Bizhi Shi, Yanyu Bi, Huamao Wang, Hongyang Wang, Zonghai Li
Adoptive immunotherapy leveraging chimeric antigen receptor-modified T (CAR-T) cells holds great promise for the treatment of cancer. However, tumor-associated antigens often have low expression levels in normal tissues, which can cause on-target, off-tumor toxicity. Recently, we reported that GPC3-targeted CAR-T cells could eradicate hepatocellular carcinoma (HCC) xenografts in mice. However, it remains unknown whether on-target, off-tumor toxicity can occur. Therefore, we proposed that dual-targeted CAR-T cells co-expressing glypican-3 (GPC3) and asialoglycoprotein receptor 1 (ASGR1) (a liver tissue-specific protein)-targeted CARs featuring CD3ζ and 28BB (containing both CD28 and 4-1BB signaling domains), respectively, may have reduced on-target, off-tumor toxicity...
December 29, 2016: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28035063/perioperative-plasma-glypican-3-level-may-enable-prediction-of-the-risk-of-recurrence-after-surgery-in-patients-with-stage-i-hepatocellular-carcinoma
#7
Kazuya Ofuji, Keigo Saito, Shiro Suzuki, Manami Shimomura, Hirofumi Shirakawa, Daisuke Nobuoka, Yu Sawada, Mayuko Yoshimura, Nobuhiro Tsuchiya, Mari Takahashi, Toshiaki Yoshikawa, Yoshitaka Tada, Masaru Konishi, Shinichiro Takahashi, Naoto Gotohda, Yasunari Nakamoto, Tetsuya Nakatsura
Glypican-3 (GPC3) is a glycosylphosphatidylinositol-anchored cell surface protein overexpressed in hepatocellular carcinoma(HCC), and its overexpression is associated with poor prognosis. The diagnostic potential of GPC3 as a serum marker has been reported. In the present study, we evaluated the usefulness of plasma GPC3 as a predictor for recurrence after surgical resection in stage I HCC patients by newly developed an enzyme-linked immunosorbent assay (ELISA) system. Current study demonstrated that high levels of preoperative plasma GPC3 patients tended to experience postoperative recurrence...
December 27, 2016: Oncotarget
https://www.readbyqxmd.com/read/27999758/efficacy-of-glypican-3-derived-peptide-vaccine-therapy-on-the-survival-of-patients-with-refractory-ovarian-clear-cell-carcinoma
#8
Shiro Suzuki, Jun Sakata, Fumi Utsumi, Ryuichiro Sekiya, Hiroaki Kajiyama, Kiyosumi Shibata, Fumitaka Kikkawa, Tetsuya Nakatsura
Compared with other epithelial ovarian carcinoma subtypes, ovarian clear cell carcinoma (OCCC) has been recognized to show chemoresistance. Therefore, new treatment modalities are required for patients with OCCC that is refractory to chemotherapy. The carcinoembryonic antigen glypican-3 (GPC3) is expressed by approximately half of OCCC and is a promising immunotherapeutic target. The purpose of this study was to evaluate the effect of GPC3 peptide vaccine against refractory OCCC patients. We conducted a phase II trial with a GPC3-derived peptide vaccine in OCCC patients...
2016: Oncoimmunology
https://www.readbyqxmd.com/read/27878117/gpc-3-in-hepatocellular-carcinoma-current-perspectives
#9
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
#10
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
#11
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
#12
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
#13
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...
January 2017: 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
#14
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
#15
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
#16
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
#17
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...
2016: Cancer Biomarkers: Section A of Disease Markers
https://www.readbyqxmd.com/read/27669301/glypican-3-targeting-immunotoxins-for-the-treatment-of-liver-cancer
#18
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
#19
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
#20
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
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