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https://www.readbyqxmd.com/read/28211170/endothelial-glycocalyx-as-a-critical-signalling-platform-integrating-the-extracellular-haemodynamic-forces-and-chemical-signalling
#1
REVIEW
Ye Zeng
The glycocalyx covers the human mammalian cells and plays important roles in stroke, inflammation and atherosclerosis. It has also been shown to be involved in endothelial mechanotransduction of shear stress. Shear stress induces the remodelling of the major component of the glycocalyx including glypican-1, a cell membrane heparan sulphate proteoglycan. Other factors, such as sphingosine-1-phosphate (S1P), protect the glycocalyx against syndecan-1 ectodomain shedding and induce the synthesis of heparan sulphate...
February 17, 2017: Journal of Cellular and Molecular Medicine
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/28192166/detailed-expression-profile-of-the-six-glypicans-and-their-modifying-enzyme-notum-during-chick-limb-and-feather-development
#4
Kawakeb Saad, Susanne Theis, Anthony Otto, Graham Luke, Ketan Patel
The development of vertebrate appendages, especially the limb and feather buds are orchestrated by numerous secreted signalling molecules including Sonic Hedgehog, Bone Morphogenetic Proteins, Fibroblast Growth Factors and Wnts. These proteins coordinate the growth and patterning of ectodermal and mesenchymal cells. The influence of signalling molecules is affected over large distances by their concentration (morphogen activity) but also at local levels by the presence of proteins that either attenuate or promote their activity...
February 10, 2017: Gene
https://www.readbyqxmd.com/read/28161389/detailed-expression-profile-of-all-six-glypicans-and-their-modifying-enzyme-notum-during-chick-embryogenesis-and-their-role-in-dorsal-ventral-patterning-of-the-neural-tube
#5
Kawakeb Saad, Anthony Otto, Susanne Theis, Niki Kennerley, Andrea Munsterberg, Graham Luke, Ketan Patel
Vertebrate development is orchestrated by secreted signalling molecules that regulate cell behaviour and cell fate decisions during early embryogenesis. The activity of key signalling molecules including members of Hedgehog, Bone Morphogenetic Proteins and Wnt families are regulated by Glypicans, a family of GPI linked polypeptides. Glypicans either promote or inhibit the action of signalling molecules and add a layer of complexity that needs to be understood in order to fully decipher the processes that regulate early vertebrate development...
February 1, 2017: Gene
https://www.readbyqxmd.com/read/28130795/clinical-morphological-and-immunohistochemical-evidence-that-small-cell-carcinoma-of-the-ovary-of-hypercalcaemic-type-sccoht-may-be-a-primitive-germ-cell-neoplasm
#6
W Glenn McCluggage, Leora Witkowski, Blaise A Clarke, William D Foulkes
AIMS: The histogenesis and cell lineage of small cell carcinoma of the ovary of hypercalcaemic type (SCCOHT) is unknown. We aim to provide evidence that this may be a primitive germ cell neoplasm arising from a teratoma. METHODS/ RESULTS: Following the identification of two cases of SCCOHT associated with germ cell tumours (one dermoid cyst, one immature teratoma with a focus of yolk sac tumour), we undertook a literature review to look for any prior reports of SCCOHT in association with other neoplasms or elements...
January 28, 2017: Histopathology
https://www.readbyqxmd.com/read/28120036/phase-ib-study-of-codrituzumab-in-combination-with-sorafenib-in-patients-with-non-curable-advanced-hepatocellular-carcinoma-hcc
#7
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/28110063/curcumin-ameliorates-liver-damage-and-progression-of-nash-in-nash-hcc-mouse-model-possibly-by-modulating-hmgb1-nf-%C3%AE%C2%BAb-translocation
#8
Rejina Afrin, Somasundaram Arumugam, Azizur Rahman, Mir Imam Ibne Wahed, Vengadeshprabhu Karuppagounder, Meilei Harima, Hiroshi Suzuki, Shizuka Miyashita, Kenji Suzuki, Hiroyuki Yoneyama, Kazuyuki Ueno, Kenichi Watanabe
Curcumin, a phenolic compound, has a wide spectrum of therapeutic effects such as antitumor, anti-inflammatory, anti-cancer and so on. The study aimed to investigate the underlying mechanisms of curcumin to protect liver damage and progression of non-alcoholic steatohepatitis (NASH) in a novel NASH-hepatocellular carcinoma (HCC) mouse model. To induce this model neonatal C57BL/6J male mice were exposed to low-dose streptozotocin and were fed a high-fat diet (HFD) from the age of 4weeks to 14weeks. Curcumin was given at 100mg/kg dose daily by oral gavage started at the age of 10weeks and continued until 14weeks along with HFD feeding...
January 18, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28105114/in-utero-exposure-to-di-2-ethylhexyl-phthalate-induces-metabolic-disorder-and-increases-fat-accumulation-in-visceral-depots-of-c57bl-6j-mice-offspring
#9
Hailun Gu, Yali Liu, Wei Wang, Lifeng Ding, Weiping Teng, Li Liu
Excessive visceral fat accumulation is associated with metabolic disorders. Di-(2-ethylhexyl) phthalate (DEHP), a candidate environmental obesogen, affects lipid metabolism and adipogenesis. Perinatal exposure to DEHP may be associated with metabolic disorders of dams and offspring. The aim of the present study was to explore the effects of exposure of pregnant dams to DEHP on the metabolism and fat distribution of their offspring, and to determine the mechanisms for these effects. Pregnant C57BL/6J mice were administered DEHP via gavage (0...
December 2016: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28103900/gde2-is-essential-for-neuronal-survival-in-the-postnatal-mammalian-spinal-cord
#10
Clinton Cave, Sungjin Park, Marianeli Rodriguez, Mai Nakamura, Ahmet Hoke, Mikhail Pletnikov, Shanthini Sockanathan
BACKGROUND: Glycerophosphodiester phosphodiesterase 2 (GDE2) is a six-transmembrane protein that cleaves glycosylphosphatidylinositol (GPI) anchors to regulate GPI-anchored protein activity at the cell surface. In the developing spinal cord, GDE2 utilizes its enzymatic function to regulate the production of specific classes of motor neurons and interneurons; however, GDE2's roles beyond embryonic neurogenesis have yet to be defined. METHOD: Using a panel of histological, immunohistochemical, electrophysiological, behavioral, and biochemistry techniques, we characterized the postnatal Gde2 (-/-) mouse for evidence of degenerative neuropathology...
January 19, 2017: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/28102194/%C3%AE-3-chains-of-type-v-collagen-regulate-breast-tumour-growth-via-glypican-1
#11
Guorui Huang, Gaoxiang Ge, Valerio Izzi, Daniel S Greenspan
Pericellular α3(V) collagen can affect the functioning of cells, such as adipocytes and pancreatic β cells. Here we show that α3(V) chains are an abundant product of normal mammary gland basal cells, and that α3(V) ablation in a mouse mammary tumour model inhibits mammary tumour progression by reducing the proliferative potential of tumour cells. These effects are shown to be primarily cell autonomous, from loss of α3(V) chains normally produced by tumour cells, in which they affect growth by enhancing the ability of cell surface proteoglycan glypican-1 to act as a co-receptor for FGF2...
January 19, 2017: Nature Communications
https://www.readbyqxmd.com/read/28098909/biology-and-function-of-glypican-3-as-a-candidate-for-early-cancerous-transformation-of-hepatocytes-in-hepatocellular-carcinoma-review
#12
Mauro Montalbano, Jeremias Georgiadis, Ashlyn L Masterson, Joshua T McGuire, Janika Prajapati, Ali Shirafkan, Cristiana Rastellini, Luca Cicalese
Glypican-3 (GPC-3), a transmembrane heparan sulfate proteoglycan (HSPG), has recently been investigated as a player in tissue-dependent cellular signaling, specifically as a regulator of growth. Noteworthy, the regulatory protein has been implicated in both stimulatory and inhibitory pathways involving cell growth. Initially, GPC-3 was thought to act as a cell cycle regulator, as a loss-of-function mutation in the gene caused a hyper-proliferative state known as Simpson-Golabi-Behmel (SGB) overgrowth syndrome...
January 18, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28087980/the-significance-of-glypican-3-expression-profiling-in-the-tumor-cellular-origin-theoretical-system-for-hepatocellular-carcinoma-progression
#13
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/28075131/classical-galactosemia-insight-into-molecular-pathomechanisms-by-differential-membrane-proteomics-of-fibroblasts-under-galactose-stress
#14
Simon Staubach, Stefan Müller, Murat Pekmez, Franz-Georg Hanisch
Classical galactosemia, a hereditary metabolic disease caused by the deficiency of galactose-1-phosphate uridyltransferase (GALT; EC 2.7.712), results in an impaired galactose metabolism and serious long-term developmental affection of the CNS and ovaries, potentially related in part to endogenous galactose-induced protein dysglycosylation. In search for galactose-induced changes in membrane raft proteomes of GALT-deficient cells, we performed differential analyses of lipid rafts from patient-derived (Q) and sex- and age-matched control fibroblasts (H) in the presence or absence of the stressor...
January 24, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28050794/heterogeneity-in-synaptogenic-profile-of-astrocytes-from-different-brain-regions
#15
Andrea Schmidt Buosi, Isadora Matias, Ana Paula Bergamo Araujo, Carolina Batista, Flávia Carvalho Alcantara Gomes
Astrocytes, the most abundant glial cells in the central nervous system (CNS), comprise a heterogeneous population of cells. However, how this heterogeneity impacts their function within brain homeostasis and response to injury and disease is still largely unknown. Recently, astrocytes have been recognized as important regulators of synapse formation and maturation. Here, we analyzed the synaptogenic property of astrocytes from different regions of the CNS. The effect of conditioned medium derived from astrocytes (astrocyte-conditioned medium (ACM)) from cerebral cortex, hippocampus, midbrain and cerebellum, in synapse formation, was evaluated...
January 3, 2017: Molecular Neurobiology
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
#16
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
#17
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/28028292/glypican-3-is-useful-but-not-superior-to-hep-par-1-in-differentiating-hepatocellular-carcinoma-from-other-liver-tumours
#18
A M Pour, N Masir, I M Rose
To assess the diagnostic utility of glypican-3 (GPC-3) in comparison to Hep Par 1 in the diagnosis of liver tumours, a cross-sectional study involving 66 resected liver tumours were tested for the protein expression of these markers by immunohistochemistry using monoclonal antibodies. Of the 66 cases, 26 (39.4%) were hepatocellular carcinoma (HCC), 4 (6.1%) were intrahepatic cholangiocarcinoma and 36 (54.5%) were metastatic tumours. Hep Par 1 and GPC-3 expressions in HCC were 24/26 (92.3%) and 19/26 (73.1%) respectively...
December 2016: Malaysian Journal of Pathology
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
#19
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/27996937/comparative-genetic-screens-in-human-cells-reveal-new-regulatory-mechanisms-in-wnt-signaling
#20
Andres M Lebensohn, Ramin Dubey, Leif R Neitzel, Ofelia Tacchelly-Benites, Eungi Yang, Caleb D Marceau, Eric M Davis, Bhaven B Patel, Zahra Bahrami-Nejad, Kyle J Travaglini, Yashi Ahmed, Ethan Lee, Jan E Carette, Rajat Rohatgi
The comprehensive understanding of cellular signaling pathways remains a challenge due to multiple layers of regulation that may become evident only when the pathway is probed at different levels or critical nodes are eliminated. To discover regulatory mechanisms in canonical WNT signaling, we conducted a systematic forward genetic analysis through reporter-based screens in haploid human cells. Comparison of screens for negative, attenuating and positive regulators of WNT signaling, mediators of R-spondin-dependent signaling and suppressors of constitutive signaling induced by loss of the tumor suppressor adenomatous polyposis coli or casein kinase 1α uncovered new regulatory features at most levels of the pathway...
December 20, 2016: ELife
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