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https://www.readbyqxmd.com/read/27879288/multi-omics-analysis-of-serum-samples-demonstrates-reprogramming-of-organ-functions-via-systemic-calcium-mobilization-and-platelet-activation-in-metastatic-melanoma
#1
Besnik Muqaku, Martin Eisninger, Samuel M Meier, Ammar Tahir, Tobias Prokop, Sebastian Haferkamp, Astrid Slany, Albrecht Reichle, Christopher Gerner
Pathophysiologies of cancer-associated syndroms such as cachexia are poorly understood and no routine biomarkers have been established, yet. Using shotgun proteomics, known marker molecules including PMEL, CRP, SAA and CSPG4 were found deregulated in patients with metastatic melanoma. Targeted analysis of 58 selected proteins with multiple reaction monitoring was applied for independent data verification. In three patients, two of which suffered from cachexia, a tissue damage signature was determined, consisting of nine proteins, PLTP, CD14, TIMP1, S10A8, S10A9, GP1BA, PTPRJ, CD44 and C4A, as well as increased levels of glycine and asparagine, and decreased levels of polyunsaturated phosphatidylcholine concentrations, as determined by targeted metabolomics...
November 22, 2016: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/27812322/tamoxifen-in-the-mouse-brain-implications-for-fate-mapping-studies-using-the-tamoxifen-inducible-cre-loxp-system
#2
Martin Valny, Pavel Honsa, Denisa Kirdajova, Zdenek Kamenik, Miroslava Anderova
The tamoxifen-inducible Cre-loxP system is widely used to overcome gene targeting pre-adult lethality, to modify a specific cell population at desired time-points, and to visualize and trace cells in fate-mapping studies. In this study we focused on tamoxifen degradation kinetics, because for all genetic fate-mapping studies, the period during which tamoxifen or its metabolites remain active in the CNS, is essential. Additionally, we aimed to define the tamoxifen administration scheme, enabling the maximal recombination rate together with minimal animal mortality...
2016: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/27582000/roles-of-chondroitin-sulfate-proteoglycan-4-in-fibrogenic-adipogenic-differentiation-in-skeletal-muscle-tissues
#3
Shiho Takeuchi, Shin-Ichi Nakano, Katsuyuki Nakamura, Atsufumi Ozoe, Peggie Chien, Hidehito Yoshihara, Fumihiko Hakuno, Takashi Matsuwaki, Yasushi Saeki, Shin-Ichiro Takahashi, Keitaro Yamanouchi, Masugi Nishihara
Intramuscular adipose tissue and fibrous tissue are observed in some skeletal muscle pathologies such as Duchenne muscular dystrophy and sarcopenia, and affect muscle strength and myogenesis. They originate from common fibrogenic/adipogenic cells in the skeletal muscle. Thus, elucidating the regulatory mechanisms underlying fibrogenic/adipogenic cell differentiation is an important step toward the mediation of these disorders. Previously, we established a highly adipogenic progenitor clone, 2G11, from rat skeletal muscle and showed that basic fibroblast growth factor (bFGF) is pro-adipogenic in these cells...
October 1, 2016: Experimental Cell Research
https://www.readbyqxmd.com/read/27448975/photoimmunotheranostic-agents-for-triple-negative-breast-cancer-diagnosis-and-therapy-that-can-be-activated-on-demand
#4
Manal Amoury, Dirk Bauerschlag, Felix Zeppernick, Verena von Felbert, Nina Berges, Stefano Di Fiore, Isabell Mintert, Andreas Bleilevens, Nicolai Maass, Karen Bräutigam, Ivo Meinhold-Heerlein, Elmar Stickeler, Stefan Barth, Rainer Fischer, Ahmad Fawzi Hussain
Triple-negative breast cancer (TNBC) is a heterogeneous disease in which the tumors do not express estrogen receptor (ER), progesterone receptor (PgR) or human epidermal growth factor receptor 2 (HER2). Classical receptor-targeted therapies such as tamoxifen or trastuzumab are therefore unsuitable and combinations of surgery, chemotherapy and/or radiotherapy are required. Photoimmunotheranostics is a minimally invasive approach in which antibodies deliver nontoxic photosensitizers that emit light to facilitate diagnosis and produce cytotoxic reactive oxygen species to induce apoptosis and/or necrosis in cancer cells...
July 19, 2016: Oncotarget
https://www.readbyqxmd.com/read/27425618/mesenchymal-tumors-can-derive-from-ng2-cspg4-expressing-pericytes-with-%C3%AE-catenin-modulating-the-neoplastic-phenotype
#5
Shingo Sato, Yuning J Tang, Qingxia Wei, Makoto Hirata, Angela Weng, Ilkyu Han, Atsushi Okawa, Shu Takeda, Heather Whetstone, Puvindran Nadesan, David G Kirsch, Jay S Wunder, Benjamin A Alman
The cell of origin for most mesenchymal tumors is unclear. One cell type that contributes to this lineages is the pericyte, a cell expressing Ng2/Cspg4. Using lineage tracing, we demonstrated that bone and soft tissue sarcomas driven by the deletion of the Trp53 tumor suppressor, or desmoid tumors driven by a mutation in Apc, can derive from cells expressing Ng2/Cspg4. Deletion of the Trp53 tumor suppressor gene in these cells resulted in the bone and soft tissue sarcomas that closely resemble human sarcomas, while stabilizing β-catenin in this same cell type caused desmoid tumors...
July 26, 2016: Cell Reports
https://www.readbyqxmd.com/read/27340757/generation-of-reactive-astrocytes-from-ng2-cells-is-regulated-by-sonic-hedgehog
#6
Pavel Honsa, Martin Valny, Jan Kriska, Hana Matuskova, Lenka Harantova, Denisa Kirdajova, Lukas Valihrach, Peter Androvic, Mikael Kubista, Miroslava Anderova
NG2 cells, a fourth glial cell type in the adult mammalian central nervous system, produce oligodendrocytes in the healthy nervous tissue, and display wide differentiation potential under pathological conditions, where they could give rise to reactive astrocytes. The factors that control the differentiation of NG2 cells after focal cerebral ischemia (FCI) are largely unknown. Here, we used transgenic Cspg4-cre/Esr1/ROSA26Sortm14(CAG-tdTomato) mice, in which tamoxifen administration triggers the expression of red fluorescent protein (tomato) specifically in NG2 cells and cells derived therefrom...
September 2016: Glia
https://www.readbyqxmd.com/read/27292772/functional-roles-of-cspg4-ng2-in-chondrosarcoma
#7
Nuor S M Jamil, Asim Azfer, Harrison Worrell, Donald M Salter
CSPG4/NG2 is a multifunctional transmembrane protein with limited distribution in adult tissues including articular cartilage. The purpose of this study was to investigate the possible roles of CSPG4/NG2 in chondrosarcomas and to establish whether this molecule may have potential for targeted therapy. Stable knock-down of CSPG4/NG2 in the JJ012 chondrosarcoma cell line by shRNA resulted in decreased cell proliferation and migration as well as a decrease in gene expression of the MMP (matrix metalloproteinase) 3 protease and ADAMTS4 (aggrecanase)...
April 2016: International Journal of Experimental Pathology
https://www.readbyqxmd.com/read/27146852/prolongation-of-survival-of-dogs-with-oral-malignant-melanoma-treated-by-en-bloc-surgical-resection-and-adjuvant-cspg4-antigen-electrovaccination
#8
L A Piras, F Riccardo, S Iussich, L Maniscalco, F Gattino, M Martano, E Morello, S Lorda Mayayo, V Rolih, F Garavaglia, R De Maria, E Lardone, F Collivignarelli, D Mignacca, D Giacobino, S Ferrone, F Cavallo, P Buracco
Reported post-surgery 1-year survival rate for oral canine malignant melanoma (cMM) is around 30%; novel treatments are needed as the role of adjuvant chemotherapy is unclear. This prospective study regards adjuvant electrovaccination with human chondroitin sulfate proteoglycan-4 (hCSPG4)-encoded plasmid in 23 dogs with resected II/III-staged CSPG4-positive oral cMM compared with 19 dogs with resected only II/III-staged CSPG4-positive oral cMM. Vaccination resulted in 6-, 12-, 18- and 24-month survival rate of 95...
May 4, 2016: Veterinary and Comparative Oncology
https://www.readbyqxmd.com/read/27037627/a-novel-approach-for-targeted-elimination-of-cspg4-positive-triple-negative-breast-cancer-cells-using-a-map-tau-based-fusion-protein
#9
Manal Amoury, Radoslav Mladenov, Thomas Nachreiner, Anh-Tuan Pham, Dmitrij Hristodorov, Stefano Di Fiore, Wijnand Helfrich, Alessa Pardo, Georg Fey, Michael Schwenkert, Theophilus Thepen, Fabian Kiessling, Ahmad F Hussain, Rainer Fischer, Katharina Kolberg, Stefan Barth
Chondroitin sulfate proteoglycan 4 (CSPG4) has been identified as a highly promising target antigen for immunotherapy of triple-negative breast cancer (TNBC). TNBC represents a highly aggressive heterogeneous group of tumors lacking expression of estrogen, progesterone and human epidermal growth factor receptor 2. TNBC is particularly prevalent among young premenopausal women. No suitable targeted therapies are currently available and therefore, novel agents for the targeted elimination of TNBC are urgently needed...
August 15, 2016: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/26689475/cspg4-as-a-prognostic-biomarker-in-chordoma
#10
Andrew J Schoenfeld, Xinhui Wang, Yangyang Wang, Francis J Hornicek, G Petur Nielsen, Zhenfeng Duan, Soldano Ferrone, Joseph H Schwab
BACKGROUND: There are currently no generally accepted biomarkers used in the clinical treatment of chordoma tumors. CSPG4 has been associated with disease severity in other tumors. PURPOSE: This study aimed to characterize the frequency of CSPG4 expression in chordoma tumors and to correlate it with disease severity and clinical outcome. STUDY DESIGN: A retrospective review of clinical outcomes and immunohistochemical staining using tissue micro-array was carried out...
June 2016: Spine Journal: Official Journal of the North American Spine Society
https://www.readbyqxmd.com/read/26621608/genetic-association-of-marbling-score-with-intragenic-nucleotide-variants-at-selection-signals-of-the-bovine-genome
#11
J Ryu, C Lee
Selection signals of Korean cattle might be attributed largely to artificial selection for meat quality. Rapidly increased intragenic markers of newly annotated genes in the bovine genome would help overcome limited findings of genetic markers associated with meat quality at the selection signals in a previous study. The present study examined genetic associations of marbling score (MS) with intragenic nucleotide variants at selection signals of Korean cattle. A total of 39 092 nucleotide variants of 407 Korean cattle were utilized in the association analysis...
April 2016: Animal: An International Journal of Animal Bioscience
https://www.readbyqxmd.com/read/26469402/large-scale-purification-of-r28m-a-bispecific-scfv-antibody-targeting-human-melanoma-produced-in-transgenic-cattle
#12
Katrin Spiesberger, Florian Paulfranz, Anton Egger, Judith Reiser, Claus Vogl, Judith Rudolf-Scholik, Corina Mayrhofer, Ludger Grosse-Hovest, Gottfried Brem
BACKGROUND: 30 years ago, the potential of bispecific antibodies to engage cytotoxic T cells for the lysis of cancer cells was discovered. Today a variety of bispecific antibodies against diverse cell surface structures have been developed, the majority of them produced in mammalian cell culture systems. Beside the r28M, described here, no such bispecific antibody is known to be expressed by transgenic livestock, although various biologicals for medical needs are already harvested-mostly from the milk-of these transgenics...
2015: PloS One
https://www.readbyqxmd.com/read/26461094/targeting-human-cancer-by-a-glycosaminoglycan-binding-malaria-protein
#13
Ali Salanti, Thomas M Clausen, Mette Ø Agerbæk, Nader Al Nakouzi, Madeleine Dahlbäck, Htoo Z Oo, Sherry Lee, Tobias Gustavsson, Jamie R Rich, Bradley J Hedberg, Yang Mao, Line Barington, Marina A Pereira, Janine LoBello, Makoto Endo, Ladan Fazli, Jo Soden, Chris K Wang, Adam F Sander, Robert Dagil, Susan Thrane, Peter J Holst, Le Meng, Francesco Favero, Glen J Weiss, Morten A Nielsen, Jim Freeth, Torsten O Nielsen, Joseph Zaia, Nhan L Tran, Jeff Trent, John S Babcook, Thor G Theander, Poul H Sorensen, Mads Daugaard
Plasmodium falciparum engineer infected erythrocytes to present the malarial protein, VAR2CSA, which binds a distinct type chondroitin sulfate (CS) exclusively expressed in the placenta. Here, we show that the same CS modification is present on a high proportion of malignant cells and that it can be specifically targeted by recombinant VAR2CSA (rVAR2). In tumors, placental-like CS chains are linked to a limited repertoire of cancer-associated proteoglycans including CD44 and CSPG4. The rVAR2 protein localizes to tumors in vivo and rVAR2 fused to diphtheria toxin or conjugated to hemiasterlin compounds strongly inhibits in vivo tumor cell growth and metastasis...
October 12, 2015: Cancer Cell
https://www.readbyqxmd.com/read/26190756/chondroitin-sulfate-proteoglycan-4-as-a-target-for-chimeric-antigen-receptor-based-t-cell-immunotherapy-of-solid-tumors
#14
REVIEW
Yangyang Wang, Claudia Geldres, Soldano Ferrone, Gianpietro Dotti
INTRODUCTION: Proteoglycans are critical molecules involved in multiple physiological cell functions, but also key players in cancer development and progression. In particular, chondroitin sulfate proteoglycan 4 (CSPG4) is recognized as an attractive target for antibody-based approaches because of its high expression on cancer cells in several types of human malignancies and its restricted distribution in normal tissues. AREAS COVERED: Adoptive transfer of genetically modified T cells is emerging as a powerful therapeutic approach in cancer patients...
2015: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/25997619/anti-chondroitin-sulfate-proteoglycan-4-specific-antibodies-modify-the-effects-of-vemurafenib-on-melanoma-cells-differentially-in-normoxia-and-hypoxia
#15
Daniela Pucciarelli, Nina Lengger, Martina Takacova, Lucia Csaderova, Maria Bartosova, Heimo Breiteneder, Silvia Pastorekova, Christine Hafner
Chondroitin sulfate proteoglycan 4 (CSPG4), a highly immunogenic melanoma tumor antigen, is a potential target for antibody-based immunotherapy. The mechanism by which CSPG4 affects melanoma progression is only partly understood, in particular the involvement of other receptor tyrosine kinases and the tumor microenvironment. We have previously reported on a mimotope-based vaccine against CSPG4 in a human melanoma xenograft model that resulted in reduction of tumor growth. Herein we describe the influence of hypoxia on the response to polyclonal anti-CSPG4-antibodies induced by this vaccine in combination with the BRAF inhibitor vemurafenib to enhance therapeutic efficacy by simultaneously targeting multiple signaling pathways...
July 2015: International Journal of Oncology
https://www.readbyqxmd.com/read/25935541/proteoglycan-based-diversification-of-disease-outcome-in-head-and-neck-cancer-patients-identifies-ng2-cspg4-and-syndecan-2-as-unique-relapse-and-overall-survival-predicting-factors
#16
Anna Farnedi, Silvia Rossi, Nicoletta Bertani, Mariolina Gulli, Enrico Maria Silini, Maria Teresa Mucignat, Tito Poli, Enrico Sesenna, Davide Lanfranco, Lucio Montebugnoli, Elisa Leonardi, Claudio Marchetti, Renato Cocchi, Andrea Ambrosini-Spaltro, Maria Pia Foschini, Roberto Perris
BACKGROUND: Tumour relapse is recognized to be the prime fatal burden in patients affected by head and neck squamous cell carcinoma (HNSCC), but no discrete molecular trait has yet been identified to make reliable early predictions of tumour recurrence. Expression of cell surface proteoglycans (PGs) is frequently altered in carcinomas and several of them are gradually emerging as key prognostic factors. METHODS: A PG expression analysis at both mRNA and protein level, was pursued on primary lesions derived from 173 HNSCC patients from whom full clinical history and 2 years post-surgical follow-up was accessible...
2015: BMC Cancer
https://www.readbyqxmd.com/read/25805311/photochemical-internalisation-a-minimally-invasive-strategy-for-light-controlled-endosomal-escape-of-cancer-stem-cell-targeting-therapeutics
#17
REVIEW
Pål Kristian Selbo, Monica Bostad, Cathrine Elisabeth Olsen, Victoria Tudor Edwards, Anders Høgset, Anette Weyergang, Kristian Berg
Despite progress in radio-, chemo- and photodynamic-therapy (PDT) of cancer, treatment resistance still remains a major problem for patients with aggressive tumours. Cancer stem cells (CSCs) or tumour-initiating cells are intrinsically and notoriously resistant to conventional cancer therapies and are proposed to be responsible for the recurrence of tumours after therapy. According to the CSC hypothesis, it is imperative to develop novel anticancer agents or therapeutic strategies that take into account the biology and role of CSCs...
August 2015: Photochemical & Photobiological Sciences
https://www.readbyqxmd.com/read/25767619/theranostic-impact-of-ng2-cspg4-proteoglycan-in-cancer
#18
REVIEW
Pier Andrea Nicolosi, Alice Dallatomasina, Roberto Perris
NG2/CSPG4 is an unusual cell-membrane integral proteoglycan widely recognized to be a prognostic factor, a valuable tool for ex vivo and non-invasive molecular diagnostics and, by virtue of its tight association with malignancy, a tantalizing therapeutic target in several tumour types. Although the biology behind its involvement in cancer progression needs to be better understood, implementation of NG2/CSPG4 in the routine clinical practice is attainable and has the potential to contribute to an improved individualized management of cancer patients...
2015: Theranostics
https://www.readbyqxmd.com/read/25750275/chondroitin-sulfate-proteoglycan-4-does-not-protect-melanoma-cells-during-inhibition-of-pi3k-and-mtor-pathways
#19
Sehrish Javaid, Kaoru Terai, Arkadiusz Z Dudek
BACKGROUND: Chondroitin sulfate proteoglycan-4 (CSPG4) is commonly expressed in melanoma cells and induces melanoma cell proliferation and migration by enhancement of activation of the extracellular signal-regulated kinase 1, 2 (ERK1,2) pathway. The phosphoinositide 3-kinase (PI3K) -protein kinase B (AKT) and mammalian target of rapamycin (mTOR) pathways are also frequently de-regulated in melanoma. We hypothesized that CSPG4, by sustained activation of PI3K, may reduce the effect of the dual inhibition of PI3K-AKT and mTOR pathways...
March 2015: Anticancer Research
https://www.readbyqxmd.com/read/25715761/proteoglycans-as-potential-microenvironmental-biomarkers-for-colon-cancer
#20
Anastasia V Suhovskih, Svetlana V Aidagulova, Vladimir I Kashuba, Elvira V Grigorieva
Glycosylation changes occur widely in colon tumours, suggesting glycosylated molecules as potential biomarkers for colon cancer diagnostics. In this study, proteoglycans (PGs) expression levels and their transcriptional patterns are investigated in human colon tumours in vivo and carcinoma cells in vitro. According to RT-PCR analysis, normal and cancer colon tissues expressed a specific set of PGs (syndecan-1, perlecan, decorin, biglycan, versican, NG2/CSPG4, serglycin, lumican, CD44), while the expression of glypican-1, brevican and aggrecan was almost undetectable...
September 2015: Cell and Tissue Research
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