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https://www.readbyqxmd.com/read/28445973/plasmodium-parasite-as-an-effective-hepatocellular-carcinoma-antigen-glypican-3-delivery-vector
#1
Quan Liu, Yijun Yang, Xuefang Tan, Zhu Tao, Dickson Adah, Songlin Yu, Junnan Lu, Siting Zhao, Limei Qin, Li Qin, Xiaoping Chen
We have previously demonstrated that malaria parasite infection has an anti-tumor effect in a mouse model. This research aimed to investigate the possibility of using Plasmodium parasite as a novel vaccine vector for hepatocellular carcinoma (HCC) immunotherapy. We constructed a Plasmodium yoelii 17XNL strain (P.y) expressing murine glypican-3 (GPC3) protein (P.y-GPC3), and examined its therapeutic potency in a murine Hepa1-6-induced hepatoma model that highly expressed GPC3 protein. The prerequisites for invoking a CD8+ T cell response were assessed after P...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28429175/development-of-a-time-resolved-fluorescence-immunoassay-for-the-diagnosis-of-hepatocellular-carcinoma-based-on-the-detection-of-glypican-3
#2
Juan-Juan Chen, Chun-Mei Xie, Cong-Rong Wang, Yong Wan, Zhi-Ning Dong, Ming Li, Wei-Wen Xu
Glypican-3(GPC3), an oncofetal protein, is a potential novel marker for hepatocellular carcinoma (HCC). In this study, we attempted to establish a new method to detect serum GPC3 using the antibodies identified in our previous research, and then evaluated its clinical application for the diagnosis of HCC. Herein, a sandwich time-resolved fluorescence immunoassay (TRFIA) for detecting serum GPC3 was developed. The detection limit, analytical recovery, specificity and precision of the proposed TRFIA assay were satisfactory...
April 20, 2017: Journal of Fluorescence
https://www.readbyqxmd.com/read/28426184/alterations-in-mandibular-morphology-associated-with-glypican-1-and-glypican-3-gene-mutations
#3
M Mian, S Ranjitkar, G C Townsend, P J Anderson
OBJECTIVES: Glypican 1 (GPC1) and glypican 3 (GPC3) are bone co-regulators that act downstream in many of the signalling pathways associated with craniosynostosis. Morphometric data from GPC-knockout mice were analysed to determine whether elimination of GPC1 and GPC3 genes would alter mandibular morphology. SETTING AND SAMPLE POPULATION: The murine model included five male and five female mandibles in each of GPC1-knockout, GPC1/GPC3-knockout and wild-type (control) groups...
April 20, 2017: Orthodontics & Craniofacial Research
https://www.readbyqxmd.com/read/28386563/the-effect-of-phototherapy-on-cancer-predisposition-genes-of-diabetic-and-normal-human-skin-fibroblasts
#4
Pongsathorn Chotikasemsri, Boonsin Tangtrakulwanich, Surasak Sangkhathat
The purpose of this study was to investigate whether LED light at different wavelengths affects the expression profile of 143 cancer predisposition genes in both diabetic and normal human fibroblasts. In this study, both diabetic and normal fibroblast cell lines were cultured and irradiated with red (635 nm), green (520 nm), and blue (465 nm) LED light for 10 minutes at 0.67 J/cm(2) each. After that, mRNA from all cell lines was extracted for microarray analysis. We found that green light activates EPHB2, KIT, ANTXR2, ESCO2, MSR1, EXT1, TSC1, KIT, NF1, BUB1B, FANCD2, EPCAM, FANCD2, NF, DIS3L2, and RET in normal fibroblast cells, while blue and red light can upregulate RUNX1, PDGFRA, EHBP1, GPC3, AXIN2, KDR, GLMN, MSMB, EPHB2, MSR1, KIT, FANCD2, BMPR1A, BUB1B, PDE11A, and RET...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28378832/glypican-3-as-a-serum-marker-for-hepatoblastoma
#5
Shengmei Zhou, Maurice R G O'Gorman, Fusheng Yang, Kevin Andresen, Larry Wang
Hepatoblastoma (HB) is the most common primary liver cancer in children. The conventional serum marker for HB, alpha-fetoprotein (AFP), has its limitations. Novel serum markers need to be explored. Glypican 3 (GPC3) has been reported to be an excellent histological immunomarker for HB. However, the clinical value of serum GPC3 in patients with HB is unknown. A total of 184 serum samples were tested for both GPC3 by ELISA, and AFP by immunometric assay. Of these, 134 were from 32 patients with HB at three treatment stages, 30 from age-matched patients with benign hepatobiliary disorders (BHD) and 20 from age-matched "normal controls"(NC)...
April 5, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28371070/molecular-analysis-of-a-novel-intragenic-deletion-in-gpc3-in-three-cousins-with-simpson-golabi-behmel-syndrome
#6
Julia Schmidt, Ronja Hollstein, Frank J Kaiser, Gabriele Gillessen-Kaesbach
Simpson-Golabi-Behmel syndrome (SGBS) is characterized by multiple congenital abnormalities, pre/postnatal overgrowth, distinctive craniofacial features intellectual disability (ID) of variable degree, and an increased risk for embryonal tumors. SGBS is X-linked recessive and caused by deletions, duplications, and point mutations in GPC3, encoding a membrane associated cell surface heparan sulfate proteoglycan named glypican 3. GPC3 plays essential roles in the regulation of cell growth signaling and cell division...
March 29, 2017: American Journal of Medical Genetics. Part A
https://www.readbyqxmd.com/read/28368009/entire-cd3%C3%AE%C2%B5-%C3%AE-and-%C3%AE-humanized-mouse-to-evaluate-human-cd3-mediated-therapeutics
#7
Otoya Ueda, Naoko A Wada, Yasuko Kinoshita, Hiroshi Hino, Mami Kakefuda, Tsuneo Ito, Etsuko Fujii, Mizuho Noguchi, Kiyoharu Sato, Masahiro Morita, Hiromi Tateishi, Kaoru Matsumoto, Chisato Goto, Yosuke Kawase, Atsuhiko Kato, Kunihiro Hattori, Junichi Nezu, Takahiro Ishiguro, Kou-Ichi Jishage
T cell-mediated immunotherapy is an attractive strategy for treatment in various disease areas. In this therapeutic approach, the CD3 complex is one of the key molecules to modulate T cell functions; however, in many cases, we cannot evaluate the drug candidates in animal experiments because the therapeutics, usually monoclonal antibodies specific to human CD3, cannot react to mouse endogenous Cd3. Although immunodeficient mice transfused with human hematopoietic stem or precursor cells, known as humanized mice, are available for these studies, mice humanized in this manner are not completely immune competent...
April 3, 2017: Scientific Reports
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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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