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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
#1
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
#2
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
#3
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
#4
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
#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/28075131/classical-galactosemia-insight-into-molecular-pathomechanisms-by-differential-membrane-proteomics-of-fibroblasts-under-galactose-stress
#6
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 11, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28050794/heterogeneity-in-synaptogenic-profile-of-astrocytes-from-different-brain-regions
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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, sensitizing and positive regulators of WNT signaling, mediators of R-spondin-dependent signaling and suppressors of constitutive signaling induced by loss of the tumor suppressor APC or casein kinase 1α uncovered new regulatory features at many levels of the pathway...
December 20, 2016: ELife
https://www.readbyqxmd.com/read/27984126/malignant-transformation-of-a-b-catenin-inflammatory-adenoma-due-to-a-s45-%C3%A3-catenin-activating-mutation-present-12-years-before
#13
Christine Sempoux, Bettina Bisig, Gabrielle Couchy, Charles Balabaud, Jessica Zucman-Rossi, Paulette Bioulac-Sage
In 1984, a 24-year-old woman underwent a right hepatectomy following a 17 cm nodule, diagnosed as a hepatocellular adenoma with some atypia. The resection was incomplete. Follow-up was interrupted. In 1996, a computed tomography scan revealed a large multifocal hepatocellular carcinoma (HCC) confirmed on biopsies. The patient died the same year. We reviewed these nodules using immunohistochemistry and gene sequencing. CRP was overexpressed in the tumor resected in 1984. Glutamine synthetase (GS) was heterogeneous in the tumor with few tumor nuclei expressing ß-catenin...
October 28, 2016: Human Pathology
https://www.readbyqxmd.com/read/27960089/glycerophosphodiesterase-gde2-promotes-neuroblastoma-differentiation-through-glypican-release-and-is-a-marker-of-clinical-outcome
#14
Elisa Matas-Rico, Michiel van Veen, Daniela Leyton-Puig, Jeroen van den Berg, Jan Koster, Katarzyna M Kedziora, Bas Molenaar, Marjolein J A Weerts, Iris de Rink, René H Medema, Ben N G Giepmans, Anastassis Perrakis, Kees Jalink, Rogier Versteeg, Wouter H Moolenaar
No abstract text is available yet for this article.
December 12, 2016: Cancer Cell
https://www.readbyqxmd.com/read/27955748/influence-of-bioactive-sulfated-polysaccharide-protein-complexes-on-hepatocarcinogenesis-angiogenesis-and-immunomodulatory-activities
#15
Azza A Matloub, Hadeer A Aglan, Sahar Salah Mohamed El Souda, Mona Elsayed Aboutabl, Amany Sayed Maghraby, Hanaa H Ahmed
OBJECTIVE: To explore the in vivo anticancer, anti-angiogenesis and immunomodulatory efficacies of the bioactive polysaccharide isolated from cold aqueous extract of Jania rubens (JCEM) and Pterocladia capillacea (PCEM) as well as hot aqueous extract of Enteromorpha intestinalis (EHEM) against hepatocellular carcinoma rat model (HCC) and to study their chemical composition. METHODS: The sugars and amino acids composition of the bioactive polysaccharides of JCEM, PCEM and EHEM were determined using gas liquid chromatography and amino acid analyzer, respectively...
December 2016: Asian Pacific Journal of Tropical Medicine
https://www.readbyqxmd.com/read/27951474/down-regulation-of-fibroblast-growth-factor-2-and-its-co-receptors-heparan-sulfate-proteoglycans-by-resveratrol-underlies-the-improvement-of-cardiac-dysfunction-in-experimental-diabetes
#16
Célia Maria Cássaro Strunz, Alessandra Roggerio, Paula Lázara Cruz, Ana Paula Pacanaro, Vera Maria Cury Salemi, Luiz Alberto Benvenuti, Antonio de Pádua Mansur, Maria Cláudia Irigoyen
Cardiac remodeling in diabetes involves cardiac hypertrophy and fibrosis, and fibroblast growth factor 2 (FGF2) is an important mediator of this process. Resveratrol, a polyphenolic antioxidant, reportedly promotes the improvement of cardiac dysfunction in diabetic rats. However, little information exists linking the amelioration of the cardiac function promoted by resveratrol and the expression of FGF2 and its co-receptors, heparan sulfate proteoglycans (HSPGs: Glypican-1 and Syndecan-4), in cardiac muscle of Type 2 diabetic rats...
December 2, 2016: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/27895553/glypican-6-enhances-n-methyl-d-aspartate-receptor-function-in-human-induced-pluripotent-stem-cell-derived-neurons
#17
Kaoru Sato, Kanako Takahashi, Yukari Shigemoto-Mogami, Kaori Chujo, Yuko Sekino
The in vitro use of neurons that are differentiated from human induced pluripotent stem cells (hiPSC-neurons) is expected to improve the prediction accuracy of preclinical tests for both screening and safety assessments in drug development. To achieve this goal, hiPSC neurons are required to differentiate into functional neurons that form excitatory networks and stably express N-methyl-D-aspartate receptors (NMDARs). Recent studies have identified some astrocyte-derived factors that are important for the functional maturation of neurons...
2016: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/27878658/role-of-matricellular-proteins-in-disorders-of-the-central-nervous-system
#18
A R Jayakumar, A Apeksha, M D Norenberg
Matricellular proteins (MCPs) are actively expressed non-structural proteins present in the extracellular matrix, which rapidly turnover and possess regulatory roles, as well as mediate cell-cell interactions. MCPs characteristically contain binding sites for other extracellular proteins, cell surface receptors, growth factors, cytokines and proteases, that provide structural support for surrounding cells. MCPs are present in most organs, including brain, and play a major role in cell-cell interactions and tissue repair...
November 23, 2016: Neurochemical Research
https://www.readbyqxmd.com/read/27878117/gpc-3-in-hepatocellular-carcinoma-current-perspectives
#19
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
#20
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
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