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Glypican

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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/29118993/cellular-characteristics-of-keratin-19-positive-canine-hepatocellular-tumours-explain-its-aggressive-behaviour
#2
Renee G van Sprundel, Ted Sgam van den Ingh, Baukje A Schotanus, Monique E van Wolferen, Louis C Penning, Jan Rothuizen, Bart Spee
The expression of the hepatic progenitor cell marker keratin 19 (K19) in canine hepatocellular carcinomas is linked with a poor prognosis. To better understand this aggressive behaviour, K19-positive hepatocellular carcinomas (n=5) and K19-negative hepatocellular adenomas (n=6) were immunohistochemically stained for proteins involved in malignant tumour development. The K19-positive carcinomas showed marked positivity for platelet-derived growth factor receptor alpha polypeptide (PDGFRα), laminin, integrin beta-1/CD29, B-cell-specific Moloney murine leukaemia virus Integration site 1, glypican-3 (GPC-3) and prominin-1/CD133, in contrast with K19-negative hepatocellular adenomas...
2017: Veterinary Record Open
https://www.readbyqxmd.com/read/29114039/neuronal-activity-drives-fmrp-and-hspg-dependent-matrix-metalloproteinase-function-required-for-rapid-synaptogenesis
#3
Mary L Dear, Jarrod Shilts, Kendal Broadie
Matrix metalloproteinase (MMP) functions modulate synapse formation and activity-dependent plasticity. Aberrant MMP activity is implicated in fragile X syndrome (FXS), a disease caused by the loss of the RNA-binding protein FMRP and characterized by neurological dysfunction and intellectual disability. Gene expression studies in Drosophila suggest that Mmps cooperate with the heparan sulfate proteoglycan (HSPG) glypican co-receptor Dally-like protein (Dlp) to restrict trans-synaptic Wnt signaling and that synaptogenic defects in the fly model of FXS are alleviated by either inhibition of Mmp or genetic reduction of Dlp...
November 7, 2017: Science Signaling
https://www.readbyqxmd.com/read/29113314/glypican-3-induces-oncogenicity-by-preventing-igf-1r-degradation-a-process-that-can-be-blocked-by-grb10
#4
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/29106744/germ-cell-tumor-growth-patterns-originating-from-clear-cell-carcinomas-of-the-ovary-and-endometrium-a-comparative-immunohistochemical-study-favouring-their-origin-from-somatic-stem-cells
#5
F F Nogales, J Prat, M Schuldt, N Cruz-Viruel, B Kau, E D'Angelo, X Matias-Guiu, A Vidal, W G McCluggage, J W Oosterhuis
AIMS: To report a series of 11 ovarian and one endometrial neoplasm in elderly patients with mixed clear cell tumour and germ cell tumour (GCT) components, to compare their immunohistochemical and demonstrate a putative stem cell population. METHODS AND RESULTS: The clear cell tumours included 11 clear cell carcinomas (CCC) and 1 borderline clear cell tumour, while the GCT always included glandular yolk sac tumour (YST). In 4 cases, there were also foci of teratoma with immature neuroepithelial and endodermal tissues, and undifferentiated areas showing true embryoids...
November 6, 2017: Histopathology
https://www.readbyqxmd.com/read/29097878/high-grade-myofibroblastic-sarcoma-in-the-liver-a-case-report
#6
Jun Wen, Wei Zhao, Chuan Li, Jun-Yi Shen, Tian-Fu Wen
Only two cases of myofibroblastic sarcoma in the liver have been reported in the literature. Here, we report the case of a male patient with high-grade myofibroblastic sarcoma mimicking echinococcosis in the liver. The 25-year-old male patient complained of right upper quadrant swelling pain for one week and was initially diagnosed with echinococcosis. He was then scheduled for an exploratory laparotomy. During the operation, a huge mass exceeding 16 cm in diameter was found to occupy nearly the entire right trisegment of the liver, with a clear boundary and a round shape, and the mass was resected by right hepatic trisegmentectomy...
October 14, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/29089873/exploiting-heparan-sulfate-proteoglycans-in-human-neurogenesis-controlling-lineage-specification-and-fate
#7
REVIEW
Chieh Yu, Lyn R Griffiths, Larisa M Haupt
Unspecialized, self-renewing stem cells have extraordinary application to regenerative medicine due to their multilineage differentiation potential. Stem cell therapies through replenishing damaged or lost cells in the injured area is an attractive treatment of brain trauma and neurodegenerative neurological disorders. Several stem cell types have neurogenic potential including neural stem cells (NSCs), embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs), and mesenchymal stem cells (MSCs). Currently, effective use of these cells is limited by our lack of understanding and ability to direct lineage commitment and differentiation of neural lineages...
2017: Frontiers in Integrative Neuroscience
https://www.readbyqxmd.com/read/29081389/toxoplasma-gondii-ron4-binds-to-heparan-sulfate-on-the-host-cell-surface
#8
Hitoshi Takemae, Kyousuke Kobayashi, Tatsuki Sugi, Yongmei Han, Haiyan Gong, Akiko Ishiwa, Frances C Recuenco, Fumi Murakoshi, Ryo Takano, Yuho Murata, Kisaburo Nagamune, Taisuke Horimoto, Hiroomi Akashi, Kentaro Kato
Toxoplasma gondii rhoptry neck protein 4 (TgRON4) is a component of the moving junction, a key structure for host cell invasion. We previously showed that host cellular β-tubulin is a binding partner of TgRON4 in the invasion process. Here, to identify other binding partners of TgRON4 in the host cell, we examined the binding of TgRON4 to components of the host cell surface. TgRON4 binds to various mammalian cells, but this binding disappeared in glycosaminoglycan- and heparan sulfate-deficient CHO cells and after heparitinase treatment of mammalian cells...
October 25, 2017: Parasitology International
https://www.readbyqxmd.com/read/29077109/a-novel-rapid-and-sensitive-homogeneous-sandwich-detection-method-of-glypican-3-as-a-serum-marker-for-hepatocellular-carcinoma
#9
Naihan Han, Wenshuang Wang, Danrong Lu, Han Wang, Xinying Ma, Xiaopeng Fan, Fuchuan Li
Based on multiple interactions and fluorescence quenching, we report a novel homogeneous detection method for Glypican-3 which shows a series of significant advantages, including low cost, ease of preparation, rapid response, and high sensitivity and has great potential in the clinical diagnosis of hepatocellular carcinoma and proteoglycan detection.
October 27, 2017: Chemical Communications: Chem Comm
https://www.readbyqxmd.com/read/29073605/n-cadherin-maintains-the-healthy-biology-of-nucleus-pulposus-cells-under-high-magnitude-compression
#10
Zhenyu Wang, Jiali Leng, Yuguang Zhao, Dehai Yu, Feng Xu, Qingxu Song, Zhigang Qu, Xinming Zhuang, Yi Liu
BACKGROUND/AIMS: Mechanical load can regulate disc nucleus pulposus (NP) biology in terms of cell viability, matrix homeostasis and cell phenotype. N-cadherin (N-CDH) is a molecular marker of NP cells. This study investigated the role of N-CDH in maintaining NP cell phenotype, NP matrix synthesis and NP cell viability under high-magnitude compression. METHODS: Rat NP cells seeded on scaffolds were perfusion-cultured using a self-developed perfusion bioreactor for 5 days...
October 27, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29065163/drosophila-vamp7-regulates-wingless-intracellular-trafficking
#11
Han Gao, Fang He, Xinhua Lin, Yihui Wu
Drosophila Wingless (Wg) is a morphogen that determines cell fate during development. Previous studies have shown that endocytic pathways regulate Wg trafficking and signaling. Here, we showed that loss of vamp7, a gene required for vesicle fusion, dramatically increased Wg levels and decreased Wg signaling. Interestingly, we found that levels of Dally-like (Dlp), a glypican that can interact with Wg to suppress Wg signaling at the dorsoventral boundary of the Drosophila wing, were also increased in vamp7 mutant cells...
2017: PloS One
https://www.readbyqxmd.com/read/29065111/identification-of-a-specific-peptide-binding-to-colon-cancer-cells-from-a-phage-displayed-peptide-library
#12
Lidan Hou, Danxi Zhu, Yu Liang, Xiaohui Tian, Lei Li, Ping Wang, Liming Zhu, Xiaoling Weng, Yingying Wang, Yue Li, Tianqi Wu, Jianhua Wang, Xiangjun Meng
BACKGROUND: New molecular probes are essential for early colon cancer diagnosis. A phage-display screening was performed to select novel binding peptides for early colon cancer imaging detection. METHODS: A human colon cancer cell line (COLO320HSR) and a normal human intestinal epithelial cell line (NCM460) were used for subtractive screening with a phage peptide library. The positive peptides were identified, and their binding capacities were confirmed by confocal immunofluorescence both in human colon cancer cells and in biopsy specimens...
October 24, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/29059470/banf1-plod3-sf3b4-as-early-stage-cancer-decision-markers-and-drivers-of-hepatocellular-carcinoma
#13
Qingyu Shen, Jung Woo Eun, Kyungbun Lee, Hyung Seok Kim, Hee Doo Yang, Sang Yean Kim, Eun Kyung Lee, Taemook Kim, Keunsoo Kang, Seongchan Kim, Dal-Hee Min, Soon-Nam Oh, Young-Joon Lee, Hyuk Moon, Simon Weonsang Ro, Won Sang Park, Jung Young Lee, Suk Woo Nam
An accurate tool enabling early diagnosis of hepatocellular carcinoma (HCC) is clinically important, since early detection of HCC markedly improves survival. We aimed to investigate the molecular markers underlying early progression of HCC that can be detected in precancerous lesions. We designed a gene selection strategy to identify potential driver genes by integrative analysis of transcriptome and clinicopathologic data of human multi-stage HCC tissues including precancerous lesions, low- and high-grade dysplastic nodules...
October 23, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29055044/anti-glypican-1-antibody-drug-conjugate-exhibits-potent-preclinical-antitumor-activity-against-glypican-1-positive-uterine-cervical-cancer
#14
Satoko Matsuzaki, Satoshi Serada, Kosuke Hiramatsu, Satoshi Nojima, Shinya Matsuzaki, Yutaka Ueda, Tomoharu Ohkawara, Seiji Mabuchi, Minoru Fujimoto, Eiichi Morii, Kiyoshi Yoshino, Tadashi Kimura, Tetsuji Naka
Glypican-1 (GPC1) is highly expressed in solid tumors, especially squamous cell carcinomas (SCCs), and is thought to be associated with disease progression. We explored the use of a GPC1-targeted antibody-drug conjugate (ADC) as a novel treatment for uterine cervical cancer. On immunohistochemical staining, high expression levels of GPC1 were detected in about 50% of uterine cervical cancer tissues and also in a tumor that had relapsed after chemoradiotherapy. Novel anti-GPC1 monoclonal antibodies were developed, and clone 01a033 was selected as the best antibody for targeted delivery of the cytotoxic agent monomethyl auristatin F (MMAF) into GPC1-positive cells...
October 21, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29024665/astrocyte-secreted-glypican-4-regulates-release-of-neuronal-pentraxin-1-from-axons-to-induce-functional-synapse-formation
#15
Isabella Farhy-Tselnicker, Adriana C M van Casteren, Aletheia Lee, Veronica T Chang, A Radu Aricescu, Nicola J Allen
The generation of precise synaptic connections between developing neurons is critical to the formation of functional neural circuits. Astrocyte-secreted glypican 4 induces formation of active excitatory synapses by recruiting AMPA glutamate receptors to the postsynaptic cell surface. We now identify the molecular mechanism of how glypican 4 exerts its effect. Glypican 4 induces release of the AMPA receptor clustering factor neuronal pentraxin 1 from presynaptic terminals by signaling through presynaptic protein tyrosine phosphatase receptor δ...
October 11, 2017: Neuron
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/28970136/a-subset-of-well-differentiated-hepatocellular-carcinomas-are-arginase-1-negative
#19
Ian Clark, Sejal S Shah, Roger Moreira, Rondell P Graham, Tsung-Teh Wu, Michael S Torbenson, Vishal Chandan
Hepatocellular carcinoma (HCC) is a common malignancy both in the United States of America and worldwide. Despite the refinement of imaging techniques in at- risk populations, a needle biopsy diagnosis remains an important diagnostic tool for HCC in many cases. Various immunohistochemical markers have been developed to facilitate this diagnosis, such as HepPar-1, glypican-3 and, most recently, arginase-1. Amongst them, arginase-1 has been shown to have superior sensitivity and specificity than the others. Performance of arginase-1 has been reported to be excellent for diagnosis of well differentiated HCCs, with some tail- off in sensitivity for poorly differentiated tumors...
September 29, 2017: Human Pathology
https://www.readbyqxmd.com/read/28968990/prediction-of-early-recurrence-of-hepatocellular-carcinoma-within-the-milan-criteria-after-radical-resection
#20
Jiliang Feng, Junmei Chen, Ruidong Zhu, Lu Yu, Yan Zhang, Dezhao Feng, Heli Kong, Chenzhao Song, Hui Xia, Jushan Wu, Dawei Zhao
Approximately 50% hepatocellular carcinoma patients meeting the Milan criteria utilized to develop an improved prognostic model for predicting the recurrence in these patients. Using univariate and multivariate analysis, cytokeratin-19 and glypican-3 expression patterns, tumor number and histological grading from eight putative prognostic factors comprised the risk factor scoring model to predict the tumor recurrence. In the training cohort, the area under roc curve (AUC) value of the model was 0.715 [95% confidence interval (CI) = 0...
September 8, 2017: Oncotarget
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