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https://www.readbyqxmd.com/read/29058119/comprehensive-molecular-characterisation-of-epilepsy-associated-glioneuronal-tumours
#1
Thomas J Stone, Angus Keeley, Alex Virasami, William Harkness, Martin Tisdall, Elisa Izquierdo Delgado, Alice Gutteridge, Tony Brooks, Mark Kristiansen, Jane Chalker, Lisa Wilkhu, William Mifsud, John Apps, Maria Thom, Mike Hubank, Tim Forshew, J Helen Cross, Darren Hargrave, Jonathan Ham, Thomas S Jacques
Glioneuronal tumours are an important cause of treatment-resistant epilepsy. Subtypes of tumour are often poorly discriminated by histological features and may be difficult to diagnose due to a lack of robust diagnostic tools. This is illustrated by marked variability in the reported frequencies across different epilepsy surgical series. To address this, we used DNA methylation arrays and RNA sequencing to assay the methylation and expression profiles within a large cohort of glioneuronal tumours. By adopting a class discovery approach, we were able to identify two distinct groups of glioneuronal tumour, which only partially corresponded to the existing histological classification...
October 20, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/29054751/ng2-cspg4-and-progranulin-in-the-posttraumatic-glial-scar
#2
REVIEW
Michael K E Schäfer, Irmgard Tegeder
Traumatic injury of the central nervous system is one of the leading causes of death and disability in young adults. Failure of regeneration is caused by autonomous neuronal obstacles and by formation of the glial scar, which is essential to seal the injury but also constitutes a barrier for regrowing axons. The scar center is highly inflammatory and populated by NG2+ glia, whereas astrocytes form the sealing border and trap regrowing axons, suggesting that the non-permissive environment of activated astrocytes and extracellular matrix components is one of the reasons for the regenerative failure...
October 17, 2017: Matrix Biology: Journal of the International Society for Matrix Biology
https://www.readbyqxmd.com/read/29036679/human-recombinant-fab-fragment-from-combinatorial-libraries-of-a-b-cell-lymphoma-patient-recognizes-core-protein-of-chondroitin-sulfate-proteoglycan-4
#3
Yoko Egami, Yuta Narushima, Motohiro Ohshima, Akira Yoshida, Naruki Yoneta, Yasufumi Masaki, Kunihiko Itoh
CD antigens are well known as therapeutic targets of B-cell lymphoma. To isolate therapeutic antibodies that recognize novel targets other than CD antigens, we constructed a phage display combinatorial antibody Fab library from bone marrow lymphocytes of B-cell lymphoma patient. To eliminate antibodies reactive with known B-cell lymphoma antigen, non-hematopoietic and patient's sera reactive HeLaS3 cells was selected as a target of whole cell panning. Five rounds of panning against live HeLaS3 cells retrieved single Fab clone, termed AHSA (Antibody to HeLa Surface Antigen)...
September 28, 2017: Journal of Biochemistry
https://www.readbyqxmd.com/read/29034508/ulk4-deficiency-leads-to-hypomyelination-in-mice
#4
Min Liu, Ping Xu, Zhenlong Guan, Xiaohong Qian, Peter Dockery, Una Fitzgerald, Timothy O'Brien, Sanbing Shen
Brain nerve fibers are insulated by myelin which is produced by oligodendrocytes. Defects in myelination are increasingly recognized as a common pathology underlying neuropsychiatric and neurodevelopmental disorders, which are associated with deletions of the Unc-51-like kinase 4 (ULK4) gene. Key transcription factors have been identified for oligodendrogenesis, but little is known about their associated regulators. Here we report that Ulk4 acts as a key regulator of myelination. Myelination is reduced by half in the Ulk4(tm1a/tm1a) hypomorph brain, whereas expression of axonal marker genes Tubb3, Nefh, Nefl and Nefm remains unaltered...
January 2018: Glia
https://www.readbyqxmd.com/read/29018034/a-distinct-cellular-basis-for-early-cardiac-arrhythmias-the-cardinal-manifestation-of-arrhythmogenic-cardiomyopathy-and-the-skin-phenotype-of-cardiocutaneous-syndromes
#5
Jennifer Karmouch, Qiong Q Zhou, Christina Y Miyake, Raffaella Lombardi, Kai Kretzschmar, Marie Bannier-Hélaouët, Hans Clevers, Xander H Wehrens, James T Willerson, Ali J Marian
Rationale: Arrhythmogenic cardiomyopathy (ACM) is caused primarily by mutations in genes encoding desmosome proteins. Ventricular arrhythmias are the cardinal and typically early manifestations, whereas myocardial fibroadiposis is the pathological hallmark. Homozygous DSP (desmoplakin) and JUP (plakoglobin) mutations are responsible for a subset of ACM patients that exhibit cardiac arrhythmias and dysfunction, palmo-planter keratosis, and hair abnormalities (cardiocutaneous syndromes). Objective: To determine phenotypic consequences of deletion of Dsp in a subset of cells common to the heart and skin...
October 10, 2017: Circulation Research
https://www.readbyqxmd.com/read/28981720/selection-of-novel-affinity-matured-human-chondroitin-sulfate-proteoglycan-4-antibody-fragments-by-yeast-display
#6
Xin Yu, Liang Qu, Darell D Bigner, Vidyalakshmi Chandramohan
Chondroitin sulfate proteoglycan 4 (CSPG4) is a promising target for cancer immunotherapy due to its high level of expression in a number of malignant tumors, and its essential role in tumor growth and progression. Clinical application of CSPG4-targeting immunotherapies is hampered by the lack of fully human high-affinity CSPG4 antibodies or antibody fragments. To overcome this limitation, we performed affinity maturation on a novel human CSPG4 single-chain Fv fragment (scFv) using the random mutagenesis approach and screened for improved variants from a yeast display library using a modified whole-cell panning method followed by fluorescence-activated cell sorting...
September 1, 2017: Protein Engineering, Design & Selection: PEDS
https://www.readbyqxmd.com/read/28980450/dynamic-changes-of-urine-proteome-in-a-walker-256-tumor-bearing-rat-model
#7
Jianqiang Wu, Zhengguang Guo, Youhe Gao
Despite advances in cancer treatments, early diagnosis of cancer is still the most promising way to improve outcomes. Without homeostatic control, urine reflects systemic changes in the body and can potentially be used for early detection of cancer. In this study, a tumor-bearing rat model was established by subcutaneous injection of Walker 256 cells. Urine samples from tumor-bearing rats were collected at five time points during cancer development. Dynamic urine proteomes were profiled using liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS)...
November 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28945172/prognostic-relevance-of-ng2-cspg4-cd44-and-ki-67-in-patients-with-glioblastoma
#8
Alexandra Y Tsidulko, Galina M Kazanskaya, Diana V Kostromskaya, Svetlana V Aidagulova, Roman S Kiselev, Alexandr M Volkov, Vyacheslav V Kobozev, Alexei S Gaitan, Alexei L Krivoshapkin, Elvira V Grigorieva
Neuron-glial antigen 2 (NG2, also known as CSPG4) and hyaluronic acid receptor CD44 are chondroitin sulphate proteoglycans actively involved in brain development and its malignant transformation. Here, we aimed to compare prognostic significances of NG2, CD44 and Ki-67 expression in glioblastoma multiforme patients. Totally, 45 tissue samples and 83 paraffin-embedded tissues for 75 patients were analysed. The prognostic values of the genes were analysed using Kaplan-Meier survival curves. Grade III gliomas showed 2-fold difference in NG2 expression between anaplastic astrocytoma and oligoastrocytoma (10...
September 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28852061/cd271-determines-migratory-properties-of-melanoma-cells
#9
Josefine Radke, Florian Roßner, Torben Redmer
Melanoma cell expression of the nerve growth factor receptor CD271 is associated with stem-like properties. However, the contributing role of the receptor in melanoma cell migration is elusive. Here, we explored extracranial (skin, soft tissue, lymph node and liver, n = 13) and matched brain metastases (BM, n = 12) and observed a heterogeneous distribution of phenotypically distinct subsets of CD271(+) cells. In addition, we observed that CD271 expression gradually rises along with melanoma progression and metastasis by exploration of publicly available expression data of nevi, primary melanoma (n = 31) and melanoma metastases (n = 54)...
August 29, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28842504/functional-defects-in-clostridium-difficile-tcdb-toxin-uptake-identify-cspg4-receptor-binding-determinants
#10
Pulkit Gupta, Zhifen Zhang, Seiji N Sugiman-Marangos, John Tam, Swetha Raman, Jean-Phillipe Julien, Heather K Kroh, D Borden Lacy, Nicholas Murgolo, Kavitha Bekkari, Alex G Therien, Lorraine D Hernandez, Roman A Melnyk
Clostridium difficile is a major nosocomial pathogen that produces two exotoxins, TcdA and TcdB, with TcdB thought to be the primary determinant in human disease. TcdA and TcdB are large, multidomain proteins, each harboring a cytotoxic glucosyltransferase domain that is delivered into the cytosol from endosomes via a translocation domain after receptor-mediated endocytosis of toxins from the cell surface. Although there are currently no known host cell receptors for TcdA, three cell-surface receptors for TcdB have been identified: CSPG4, NECTIN3, and FZD1/2/7...
October 20, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28764769/anabolic-role-of-lysyl-oxidase-like-2-in-cartilage-of-knee-and-temporomandibular-joints-with-osteoarthritis
#11
Weam Alshenibr, Mustafa M Tashkandi, Saqer F Alsaqer, Yazeed Alkheriji, Amelia Wise, Sadanand Fulzele, Pushkar Mehra, Mary B Goldring, Louis C Gerstenfeld, Manish V Bais
BACKGROUND: Lysyl oxidase like-2 (LOXL2) is a copper-dependent amine oxidase. Our previous studies showed that LOXL2 is elevated during mouse fracture healing. The goal of this study was to evaluate the potential of LOXL2 to act as an anabolic agent in cartilage affected by osteoarthritis (OA). METHODS: LOXL2 was visualized in tissues from human knee and hip joints and temporomandibular joints (TMJ) by immunofluorescence. The activity of LOXL2 in human articular and TMJ chondrocytes was assessed by cell-based assays, microarray analysis, and RT-qPCR, and LOXL2-mediated activation of NF-κB and extracellular signal-related kinase (ERK) signaling pathways was measured by western blotting...
August 2, 2017: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/28668095/cspg4-a-prototype-oncoantigen-for-translational-immunotherapy-studies
#12
REVIEW
Valeria Rolih, Giuseppina Barutello, Selina Iussich, Raffaella De Maria, Elena Quaglino, Paolo Buracco, Federica Cavallo, Federica Riccardo
Thanks to striking progress in both the understanding of anti-tumor immune response and the characterization of several tumor associated antigens (TAA), a more rational design and more sophisticated strategies for anti-tumor vaccination have been possible. However, the effectiveness of cancer vaccines in clinical trial is still partial, indicating that additional studies are needed to optimize their design and their pre-clinical testing. Indeed, anti-tumor vaccination success relies on the choice of the best TAA to be targeted and on the translational power of the pre-clinical model used to assess its efficacy...
July 1, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28657611/cspg4-a-target-for-selective-delivery-of-human-cytolytic-fusion-proteins-and-trail
#13
REVIEW
Sandra Jordaan, Shivan Chetty, Neelakshi Mungra, Iris Koopmans, Peter E van Bommel, Wijnand Helfrich, Stefan Barth
Chondroitin-sulfate proteoglycan 4 (CSPG4) is a transmembrane glycoprotein overexpressed on malignant cells in several cancer types with only limited expression on normal cells. CSPG4 is implicated in several signaling pathways believed to drive cancer progression, particularly proliferation, motility and metastatic spread. Expression may serve as a prognostic marker for survival and risk of relapse in treatment-resistant malignancies including melanoma, triple negative breast cancer, rhabdomyosarcoma and acute lymphoblastic leukemia...
June 28, 2017: Biomedicines
https://www.readbyqxmd.com/read/28546458/proteoglycans-ion-channels-and-cell-matrix-adhesion
#14
REVIEW
Ioli Mitsou, Hinke A B Multhaupt, John R Couchman
Cell surface proteoglycans comprise a transmembrane or membrane-associated core protein to which one or more glycosaminoglycan chains are covalently attached. They are ubiquitous receptors on nearly all animal cell surfaces. In mammals, the cell surface proteoglycans include the six glypicans, CD44, NG2 (CSPG4), neuropilin-1 and four syndecans. A single syndecan is present in invertebrates such as nematodes and insects. Uniquely, syndecans are receptors for many classes of proteins that can bind to the heparan sulphate chains present on syndecan core proteins...
May 25, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28536635/the-regulatory-mechanisms-of-ng2-cspg4-expression
#15
REVIEW
Emmanuel Ampofo, Beate M Schmitt, Michael D Menger, Matthias W Laschke
Neuron-glial antigen 2 (NG2), also known as chondroitin sulphate proteoglycan 4 (CSPG4), is a surface type I transmembrane core proteoglycan that is crucially involved in cell survival, migration and angiogenesis. NG2 is frequently used as a marker for the identification and characterization of certain cell types, but little is known about the mechanisms regulating its expression. In this review, we provide evidence that the regulation of NG2 expression underlies inflammation and hypoxia and is mediated by methyltransferases, transcription factors, including Sp1, paired box (Pax) 3 and Egr-1, and the microRNA miR129-2...
2017: Cellular & Molecular Biology Letters
https://www.readbyqxmd.com/read/28445515/correlation-of-histopathologic-characteristics-to-protein-expression-and-function-in-malignant-melanoma
#16
Charlotte Welinder, Krzysztof Pawłowski, A Marcell Szasz, Maria Yakovleva, Yutaka Sugihara, Johan Malm, Göran Jönsson, Christian Ingvar, Lotta Lundgren, Bo Baldetorp, Håkan Olsson, Melinda Rezeli, Thomas Laurell, Elisabet Wieslander, György Marko-Varga
BACKGROUND: Metastatic melanoma is still one of the most prevalent skin cancers, which upon progression has neither a prognostic marker nor a specific and lasting treatment. Proteomic analysis is a versatile approach with high throughput data and results that can be used for characterizing tissue samples. However, such analysis is hampered by the complexity of the disease, heterogeneity of patients, tumors, and samples themselves. With the long term aim of quest for better diagnostics biomarkers, as well as predictive and prognostic markers, we focused on relating high resolution proteomics data to careful histopathological evaluation of the tumor samples and patient survival information...
2017: PloS One
https://www.readbyqxmd.com/read/28433626/thrombin-impairs-human-endometrial-endothelial-angiogenesis-implications-for-progestin-only-contraceptive-induced-abnormal-uterine-bleeding
#17
John P Shapiro, Ozlem Guzeloglu-Kayisli, Umit A Kayisli, Nihan Semerci, S Joseph Huang, Sefa Arlier, Kellie Larsen, Paolo Fadda, Frederick Schatz, Charles J Lockwood
OBJECTIVE: Progestin-only contraceptives induce abnormal uterine bleeding, accompanied by prothrombin leakage from dilated endometrial microvessels and increased thrombin generation by human endometrial stromal cell (HESC)-expressed tissue factor. Initial studies of the thrombin-treated HESC secretome identified elevated levels of cleaved chondroitin sulfate proteoglycan 4 (CSPG4), impairing pericyte-endothelial interactions. Thus, we investigated direct and CSPG4-mediated effects of thrombin in eliciting abnormal uterine bleeding by disrupting endometrial angiogenesis...
June 2017: Contraception
https://www.readbyqxmd.com/read/28287848/immunomodulating-and-immunoresistance-properties-of-cancer-initiating-cells-implications-for-the-clinical-success-of-immunotherapy
#18
REVIEW
Cristina Maccalli, Giorgio Parmiani, Soldano Ferrone
Cancer-initiating cells (CICs) represent a relatively rare subpopulation of cells endowed with self-renewal, stemness properties, tumorigenicity in immunodeficient mice, and resistance to standard therapies as well as to immunotherapy. Here, we review the biological and immunological characteristics of CICs with special focus on the immunomodulating mechanisms they utilize to escape from immunosurveillance. The recently developed immunotherapeutic strategies have yielded remarkable clinical results in many types of tumors, indicating that indeed a patient's immune system can mount an immune response, which is effective in controlling tumor growth...
April 2017: Immunological Investigations
https://www.readbyqxmd.com/read/28276839/visualization-of-vascular-mural-cells-in-developing-brain-using-genetically-labeled-transgenic-reporter-mice
#19
Bongnam Jung, Thomas D Arnold, Elisabeth Raschperger, Konstantin Gaengel, Christer Betsholtz
The establishment of a fully functional blood vascular system requires elaborate angiogenic and vascular maturation events in order to fulfill organ-specific anatomical and physiological needs. Although vascular mural cells, i.e. pericytes and vascular smooth muscle cells, are known to play fundamental roles during these processes, their characteristics during vascular development remain incompletely understood. In this report, we utilized transgenic reporter mice in which mural cells are genetically labeled to examine developing vascular mural cells in the central nervous system (CNS)...
January 1, 2017: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/28098860/chondroitin-sulfate-proteoglycan-protein-is-stimulated-by-interleukin%C3%A2-11-and-promotes-endometrial-epithelial-cancer-cell-proliferation-and-migration
#20
Amy Winship, Michelle Van Sinderen, Ariella Heffernan-Marks, Eva Dimitriadis
Endometrial cancer is the most common gynecological cancer. We identified interleukin 11 (IL11) as a critical mediator of endometrial tumourigenesis and demonstrated that IL11 regulates chondroitin sulfate proteoglycan (CSPG4) in human placental trophoblasts. CSPG4 is a cell membrane protein overexpressed in numerous human cancers, although its role in endometrial cancer has not been investigated. We examined CSPG4 expression and localization in primary human type I endometrioid grade (G) 1-3 tumours by qPCR and immunohistochemistry and determined whether IL11 stimulated CSPG4...
March 2017: International Journal of Oncology
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