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https://www.readbyqxmd.com/read/29123959/immunological-efficacy-of-glypican-3-peptide-vaccine-in-patients-with-advanced-hepatocellular-carcinoma
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
Francesco Vasuri, Deborah Malvi, Sonia Bonora, Silvia Fittipaldi, Matteo Renzulli, Francesco Tovoli, Rita Golfieri, Luigi Bolondi, Antonia D'Errico
AIMS: (i) to validate the immunohistochemical (IHC) markers Glutamine Synthetase (GS), Glypican-3 (GPC3), Heat Shock Protein-70 (HSP70) and Enhancer of Zeste homologue 2 (EZH2) on liver biopsy for the differential diagnosis between small HCC and non-neoplastic liver nodules, with special attention on <1 cm nodules; (ii) to assess the actual sensitivity and specificity of the single markers, and their combination, on needle biopsies. METHODS AND RESULTS: One-hundred (100) liver nodules, 66 HCC and 34 non-neoplastic nodules, were prospectively collected from 43 consecutive OLT patients, and subjected to "backtable" needle biopsies directly on surgical specimen...
September 7, 2017: Histopathology
https://www.readbyqxmd.com/read/28869105/correlation-between-hbv-protein-pres2-and-tumor-markers-of-hepatocellular-carcinoma
#11
Fang Luan, Bin Liu, Junguo Zhang, Shiqing Cheng, Bingchang Zhang, Yong Wang
BACKGROUND: Alpha-fetoprotein (AFP) and Glypican 3 (GPC3) are both oncogenes and reactivated in hepatocellular carcinoma (HCC). PreS2 has been proved to be an important transactivator in HCC. In this study, we aim to provide evidence that HBV protein preS2 is responsible for AFP and GPC3's reactivation in HCC. METHODS: Totally Sixty-three cases of HCC, aged 34-79, who were surgically treated and pathologically confirmed were enrolled. The levels of AFP in peripheral serum were detected with electrochemical luminescence method before surgery...
August 25, 2017: Pathology, Research and Practice
https://www.readbyqxmd.com/read/28865999/a-novel-vaccine-targeting-glypican-3-as-a-treatment-for-hepatocellular-carcinoma
#12
Qunfeng Wu, Liya Pi, Thu Le Trinh, Chaohui Zuo, Man Xia, Yu Jiao, Zhouhua Hou, Sung Jo, William Puszyk, Kien Pham, David R Nelson, Keith Robertson, David Ostrov, Pranela Rameshwar, Chang Qing Xia, Chen Liu
Hepatocellular carcinoma (HCC) has a high morbidity and mortality rate worldwide, with limited treatment options. Glypican-3 (GPC3) is a glycosylphosphatidylinositol-anchored glycoprotein that is overexpressed in most HCC tissues but not in normal tissues. GPC3-targeting antibody therapy shows limited response in a clinical trial due to the lack of a tumor-specific cytotoxic T lymphocyte (CTL) response. Here, in C57/B6 mice, we demonstrated that intravenous infusion of GPC3-coupled lymphocytes (LC/GPC3(+)) elicited robust GPC3-specific antibody and CTL responses, which effectively restricted proliferation and lysed cultured-HCC cells...
October 4, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28856237/t-cell-activating-mesenchymal-stem-cells-as-a-biotherapeutic-for-hcc
#13
Arpad Szoor, Abishek Vaidya, Mireya Paulina Velasquez, Zhuyong Mei, Daniel L Galvan, David Torres, Adrian Gee, Andras Heczey, Stephen Gottschalk
The outcome for advanced stage hepatocellular carcinoma (HCC) remains poor, highlighting the need for novel therapies. Genetically modified mesenchymal stem cells (MSCs) are actively being explored as cancer therapeutics due to their inherent ability to migrate to tumor sites. We reasoned that MSCs can be genetically modified to redirect T cells to Glypican-3 (GPC3)(+) HCC, and genetically modified these with viral vectors encoding a GPC3/CD3 bispecific T cell engager (GPC3-ENG), a bispecifc T cell engager specific for an irrelevant antigen (EGFRvIII), and/or costimulatory molecules (CD80 and 41BBL)...
September 15, 2017: Molecular Therapy Oncolytics
https://www.readbyqxmd.com/read/28852111/development-of-an-affimer-antibody-combined-immunological-diagnosis-kit-for-glypican-3
#14
Chunmei Xie, Christian Tiede, Xuanyi Zhang, Congrong Wang, Zhixiong Li, Xiao Xu, Michael J McPherson, Darren C Tomlinson, Weiwen Xu
Glypican-3 (GPC3) is a promising new marker for hepatocellular carcinoma, but the reported values for serum GPC3 differ markedly between currently available kits. Here we isolated Affimer non-antibody binding proteins against GPC3 by phage display and developed a new sandwich chemiluminescence immunoassay (CLIA) combining an Affimer with a monoclonal antibody (Affimer-MAb CLIA). The proposed CLIA assay demonstrated a wide linear range  0.03-600 ng/mL) with a good linear correlation coefficient (0.9999), a high detection limitation (0...
August 29, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28796105/overexpression-of-glypican-3-promotes-proliferation-regulates-cell-cycle-progression-and-inhibits-apoptosis-of-human-fetal-osteoblastic-cell-line-1-19
#15
Tianyi Cai, Yingzhi Wu, Ronghu Ke, Junyi Yang, Abdulsamad Ghanem, Xiongzheng Mu
Craniosynostosis is a complex disease condition, which involves premature fusion of cranial vault sutures and lacks desirable treatment. Previous studies have demonstrated decreased proliferation rate of osteoblasts and downregulated expression of glypican 3 (GPC3) in syndromic craniosynostosis patients. In this study, quantitative and qualitative analysis were utilized to assess the effect of GPC3 in human fetal osteoblastic cell line, hFOB 1.19. Lentiviral transfection efficiency with green fluorescent protein images was obtained after 72 hours...
September 2017: Journal of Craniofacial Surgery
https://www.readbyqxmd.com/read/28763861/-a-bioinformatics-analysis-of-differentially-expressed-genes-associated-with-liver-cancer
#16
W X Bai, J Gao, C Qian, X Q Zhang
Objective: To investigate differentially expressed genes associated with liver cancer using bioinformatics methods, and to screen out molecular markers for early diagnosis of liver cancer and potential molecular targets for immunotherapy. Methods: The microarray data associated with liver cancer were downloaded from Gene Expression Omnibus. JMP software was used for correlation analysis of GSE datasets, Limma program in R language was used to screen out differentially expressed genes, and the Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genome (KEGG) pathway analysis were performed for differentially expressed genes...
June 20, 2017: Zhonghua Gan Zang Bing za Zhi, Zhonghua Ganzangbing Zazhi, Chinese Journal of Hepatology
https://www.readbyqxmd.com/read/28722660/glypican-3-induces-oncogenicity-by-preventing-igf-1r-degradation-a-process-that-can-be-blocked-by-grb10
#17
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...
July 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28706134/heparin-antagonizes-cisplatin-resistance-of-a2780-ovarian-cancer-cells-by-affecting-the-wnt-signaling-pathway
#18
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. Here we aim to illuminate the underlying molecular mechanisms of LMWH in sensitizing A2780cis cells for cisplatin...
June 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28675750/expression-of-placental-regulatory-genes-is-associated-with-fetal-growth
#19
Maya A Deyssenroth, Qian Li, Marina Lacasaña, Yoko Nomura, Carmen Marsit, Jia Chen
The placenta is the principal organ regulating respiratory, nutritional, endocrine and metabolic functions on behalf of the developing fetus. Changes in gene expression patterns of placenta-specific genes may influence fetal growth. We profiled the expression of 17 genes related to placenta functioning in term placentas (n=677) to identify genes differentially expressed across birth weight categories [small (SGA), appropriate (AGA) and large (LGA) for gestational age]. ABCG2, CEBPB, CRH, GCM1, GPC3, INSL4, PGF and PLAC1 were inversely associated with LGA status, with odds ratios (ORs) and 95% confidence intervals (CI) ranging from GCM1 (OR=0...
October 26, 2017: Journal of Perinatal Medicine
https://www.readbyqxmd.com/read/28648641/glypican-based-drug-releasing-titania-implants-to-regulate-bmp2-bioactivity-as-a-potential-approach-for-craniosynostosis-therapy
#20
Manpreet Bariana, Prem Dwivedi, Sarbin Ranjitkar, John A Kaidonis, Dusan Losic, Peter J Anderson
Advances in molecular biology and nanomedicine based therapies hold promise to obviate the need of multiple surgical interventions (associated with current management) in craniosynostosis by preventing bone re-ossification. One such adjunctive therapy involves application of glypicans 1 and 3 (GPC1 and GPC3) that are BMP inhibitors implicated in downregulating the BMP2 activity in prematurely fusing sutures. Electrochemically anodized Titania nanotube (TNT) arrays have been recognized as a promising localized, long-term drug delivery platform for bone-related therapies...
June 23, 2017: Nanomedicine: Nanotechnology, Biology, and Medicine
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