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https://www.readbyqxmd.com/read/28807260/anca-in-anti-gbm-disease-moving-beyond-a-one-dimensional-clinical-phenotype
#1
Mark Canney, Mark Alan Little
McAdoo et al. propose that patients with both circulating antiglomerular basement membrane antibody and antineutrophil cytoplasm antibody demonstrate a phenotype that lies between that of single-positive antiglomerular basement membrane disease and antineutrophil cytoplasm antibody-associated vasculitis. Specifically, there may be a subset of "double-positives" that have a more favorable response to therapy. These observations, along with reports of "atypical" antiglomerular basement membrane disease, challenge us to look beyond antiglomerular basement membrane disease as a 1-dimensional entity, and better characterize its clinical spectrum...
September 2017: Kidney International
https://www.readbyqxmd.com/read/28801914/blockade-of-transforming-growth-factor-%C3%AE-signaling-enhances-oncolytic-herpes-simplex-virus-efficacy-in-patient-derived-recurrent-glioblastoma-models
#2
Shinichi Esaki, Fares Nigim, Esther Moon, Samantha Luk, Juri Kiyokawa, William Curry, Daniel P Cahill, Andrew S Chi, A John Iafrate, Robert L Martuza, Samuel D Rabkin, Hiroaki Wakimoto
Despite the current standard of multimodal management, glioblastoma (GBM) inevitably recurs and effective therapy is not available for recurrent disease. A subset of tumor cells with stem-like properties, termed GBM stem-like cells (GSCs), are considered to play a role in tumor relapse. Although oncolytic herpes simplex virus (oHSV) is a promising therapeutic for GBM, its efficacy against recurrent GBM is incompletely characterized. Transforming growth factor beta (TGF-β) plays vital roles in maintaining GSC stemness and GBM pathogenesis...
August 12, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28797294/the-anti-vascular-endothelial-growth-factor-receptor-1-monoclonal-antibody-d16f7-inhibits-invasiveness-of-human-glioblastoma-and-glioblastoma-stem-cells
#3
Maria Grazia Atzori, Lucio Tentori, Federica Ruffini, Claudia Ceci, Lucia Lisi, Elena Bonanno, Manuel Scimeca, Eskil Eskilsson, Thomas Daubon, Hrvoje Miletic, Lucia Ricci Vitiani, Roberto Pallini, Pierluigi Navarra, Rolf Bjerkvig, Stefania D'Atri, Pedro Miguel Lacal, Grazia Graziani
BACKGROUND: Glioblastoma (GBM) is a highly migratory, invasive, and angiogenic brain tumor. Like vascular endothelial growth factor-A (VEGF-A), placental growth factor (PlGF) promotes GBM angiogenesis. VEGF-A is a ligand for both VEGF receptor-1 (VEGFR-1) and VEGFR-2, while PlGF interacts exclusively with VEGFR-1. We recently generated the novel anti-VEGFR-1 monoclonal antibody (mAb) D16F7 that diminishes VEGFR-1 homodimerization/activation without affecting VEGF-A and PlGF binding. METHODS: In the present study, we evaluated the expression of VEGFR-1 in human GBM tissue samples (n = 42) by immunohistochemistry, in cell lines (n = 6) and GBM stem cells (GSCs) (n = 18) by qRT-PCR and/or western blot analysis...
August 10, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28797031/regulation-of-hypoxia-induced-autophagy-in-glioblastoma-involves-atg9a
#4
Siti Aminah Abdul Rahim, Anne Dirkse, Anais Oudin, Anne Schuster, Jill Bohler, Vanessa Barthelemy, Arnaud Muller, Laurent Vallar, Bassam Janji, Anna Golebiewska, Simone P Niclou
BACKGROUND: Hypoxia is negatively associated with glioblastoma (GBM) patient survival and contributes to tumour resistance. Anti-angiogenic therapy in GBM further increases hypoxia and activates survival pathways. The aim of this study was to determine the role of hypoxia-induced autophagy in GBM. METHODS: Pharmacological inhibition of autophagy was applied in combination with bevacizumab in GBM patient-derived xenografts (PDXs). Sensitivity towards inhibitors was further tested in vitro under normoxia and hypoxia, followed by transcriptomic analysis...
August 10, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28796467/anti-glomerular-basement-membrane-antibody-diagnostics-in-a-large-cohort-tertiary-center-should-we-trust-serological-findings
#5
Abdulla Watad, Nicola Luigi Bragazzi, Kassem Sharif, Ora Shovman, Boris Gilburd, Howard Amital, Yehuda Shoenfeld
BACKGROUND: Anti-glomerular basement membrane (GBM) antibody disease, or Goodpasture's disease, is the clinical manifestation of the production of anti-GBM antibodies, which causes rapidly progressive glomerulonephritis with or without pulmonary hemorrhage. Anti-GBM antibody detection is mandatory for the diagnosis of Goodpasture's disease either from the serum or kidney biopsy. Renal biopsy is necessary for disease confirmation; however, in cases in which renal biopsy is not possible or is delayed, serum detection of anti-GBM antibody is the only way for diagnosis...
July 2017: Israel Medical Association Journal: IMAJ
https://www.readbyqxmd.com/read/28781371/t-helper-type-17-cells-in-immune-mediated-glomerular-disease
#6
REVIEW
Christian F Krebs, Tilman Schmidt, Jan-Hendrik Riedel, Ulf Panzer
CD4(+) T cells are important drivers of tissue damage in immune-mediated renal diseases, such as anti-glomerular basement membrane glomerulonephritis, anti-neutrophil cytoplasmic antibody-associated glomerulonephritis, and lupus nephritis. The discovery of a distinct, IL-17-producing CD4(+) T-cell lineage termed T helper type 17 (TH17) cells has markedly advanced current understanding of the pathogenic mechanisms of organ-specific immunity and the pathways that lead to target organ damage. TH17 cells are characterized by the expression of the transcription factor RORγt, the production of the pro-inflammatory cytokines IL-17A, IL-17F, IL-22, and high expression of the chemokine receptor C-C-motif chemokine receptor 6 (CCR6)...
August 7, 2017: Nature Reviews. Nephrology
https://www.readbyqxmd.com/read/28765179/status-epilepticus-as-the-initial-presentation-of-antibody-negative-goodpasture-s-syndrome
#7
Ingrid Pl Ting, Sanihah Abdul Halim, Azreen Adnan, Hasnan Jaafar
Goodpasture's syndrome is a rare pulmonary-renal disease. It is characterised by presence of auto-antibodies directed against the glomerular basement membrane (GBM) antigen. These antibodies that bind to the GBM antigens cause rapidly progressive glomerulonephritis. The alveolar basement membrane also contains similar antigen, leading to pulmonary haemorrhage in active disease. We report a case of a young man who initially presented with status epilepticus and later was found to have rapidly progressive glomerulonephritis with pulmonary haemorrhage...
August 1, 2017: BMJ Case Reports
https://www.readbyqxmd.com/read/28761240/circulating-monoclonal-igg1-kappa-antibodies-causing-anti-glomerular-basement-membrane-nephritis
#8
M Vankalakunti, R Nada, A Kumar, K Patro, S Ramakrishnan, D Rangarajan
Anti-glomerular basement membrane (GBM) antibody disease is a rare but well-characterized cause of glomerulonephritis. Patients present with rapidly progressive renal failure with hemoptysis. Early diagnosis is crucial in salvaging the renal damage and life-threatening pulmonary hemorrhage. Plasmapheresis and immunosuppression is the mode of therapy. Anti-GBM antibodies are polyclonal in nature. However, rare monoclonal antibodies can cause similar destruction of glomerular capillary walls. We describe distinct combination of circulating monoclonal and anti-GBM nephritis...
July 2017: Indian Journal of Nephrology
https://www.readbyqxmd.com/read/28736431/combined-blockade-of-t-cell-immunoglobulin-and-mucin-domain-3-and-carcinoembryonic-antigen-related-cell-adhesion-molecule-1-results-in-durable-therapeutic-efficacy-in-mice-with-intracranial-gliomas
#9
Jinhu Li, Xiaodong Liu, Yijun Duan, Yueting Liu, Hongqin Wang, Shizhong Lian, Guotao Zhuang, Yimin Fan
BACKGROUND Glioblastoma multiforme (GBM) evades immune surveillance by inducing immunosuppression via receptor-ligand interactions between immune checkpoint molecules. T cell immunoglobulin and mucin domain 3 (Tim-3) is a key checkpoint receptor responsible for exhaustion and dysfunction of T cells and plays a critical role in immunosuppression. Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) has been recently identified as a heterophilic ligand for Tim-3. MATERIAL AND METHODS We established an intracranial GBM model using C57BL/6 mice and GL261 cells, and treated the mice with single or combined monoclonal antibodies (mAbs) against Tim-3/CEACAM1...
July 24, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28734730/multifaceted-c-x-c-chemokine-receptor-4-inhibition-interferes-with-anti-vascular-endothelial-growth-factor-therapy-induced-glioma-dissemination
#10
Jean-Pierre Gagner, Yasmeen Sarfraz, Valerio Ortenzi, Fawaz M Alotaibi, Luis A Chiriboga, Awab T Tayyib, Garry J Douglas, Eric Chevalier, Barbara Romagnoli, Gérald Tuffin, Michel Schmitt, Guillaume Lemercier, Klaus Dembowsky, David Zagzag
Resistance to antiangiogenic therapy glioblastoma (GBM) patients may involve hypoxia-induced expression of stromal cell-derived factor (SDF)-1α receptor C-X-C chemokine receptor 4 (CXCR4) on invading tumor, macrophage/microglial cells (MGCs), and glioma stem cells (GSCs). We determined whether antagonizing CXCR4 with peptide epitope mimetic POL5551 disrupts anti-vascular endothelial growth factor therapy-induced glioma growth and dissemination. Mice bearing orthotopic CT-2A or GL261 gliomas received POL5551 and/or anti-vascular endothelial growth factor antibody B20-4...
July 20, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28724615/glioblastoma-cellular-cross-talk-converges-on-nf-%C3%AE%C2%BAb-to-attenuate-egfr-inhibitor-sensitivity
#11
Ciro Zanca, Genaro R Villa, Jorge A Benitez, Amy Haseley Thorne, Tomoyuki Koga, Matteo D'Antonio, Shiro Ikegami, Jianhui Ma, Antonia D Boyer, Afsheen Banisadr, Nathan M Jameson, Alison D Parisian, Olesja V Eliseeva, Gabriela F Barnabe, Feng Liu, Sihan Wu, Huijun Yang, Jill Wykosky, Kelly A Frazer, Vladislav V Verkhusha, Maria G Isaguliants, William A Weiss, Timothy C Gahman, Andrew K Shiau, Clark C Chen, Paul S Mischel, Webster K Cavenee, Frank B Furnari
In glioblastoma (GBM), heterogeneous expression of amplified and mutated epidermal growth factor receptor (EGFR) presents a substantial challenge for the effective use of EGFR-directed therapeutics. Here we demonstrate that heterogeneous expression of the wild-type receptor and its constitutively active mutant form, EGFRvIII, limits sensitivity to these therapies through an interclonal communication mechanism mediated by interleukin-6 (IL-6) cytokine secreted from EGFRvIII-positive tumor cells. IL-6 activates a NF-κB signaling axis in a paracrine and autocrine manner, leading to bromodomain protein 4 (BRD4)-dependent expression of the prosurvival protein survivin (BIRC5) and attenuation of sensitivity to EGFR tyrosine kinase inhibitors (TKIs)...
July 19, 2017: Genes & Development
https://www.readbyqxmd.com/read/28716053/ibrutinib-a-bruton-s-tyrosine-kinase-inhibitor-exhibits-antitumoral-activity-and-induces-autophagy-in-glioblastoma
#12
Jin Wang, Xiaoyang Liu, Yongzhi Hong, Songtao Wang, Pin Chen, Aihua Gu, Xiaoyuan Guo, Peng Zhao
BACKGROUND: Glioblastoma (GBM) is the most common and aggressive primary brain tumor in adults. Ibrutinib, a Bruton's tyrosine kinase (BTK) inhibitor, is a novel anticancer drug used for treating several types of cancers. In this study, we aimed to determine the role of ibrutinib on GBM. METHODS: Cell proliferation was determined by using cell viability, colony formation, and 5-ethynyl-2'-deoxyuridine (EdU) assays. Cell cycle and cell apoptosis were analyzed by flow cytometry...
July 17, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28714520/genomic-profiling-of-long-non-coding-rna-and-mrna-expression-associated-with-acquired-temozolomide-resistance-in-glioblastoma-cells
#13
Huijun Zeng, Ningbo Xu, Yanting Liu, Boyang Liu, Zhao Yang, Zhao Fu, Changlin Lian, Hongbo Guo
Temozolomide (TMZ) is an alkylating chemotherapeutic agent widely used in anti-glioma treatment. However, acquired TMZ resistance represents a major clinical challenge that leads to tumor relapse or progress. This study investigated the genomic profiles including long non-coding RNA (lncRNA) and mRNA expression associated with acquired TMZ resistance in glioblastoma (GBM) cells in vitro. The TMZ-resistant (TR) of GBM sub-cell lines were established through repetitive exposure to increasing TMZ concentrations in vitro...
August 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28701209/alantolactone-a-natural-sesquiterpene-lactone-has-potent-antitumor-activity-against-glioblastoma-by-targeting-ikk%C3%AE-kinase-activity-and-interrupting-nf-%C3%AE%C2%BAb-cox-2-mediated-signaling-cascades
#14
Xun Wang, Zhenlong Yu, Chao Wang, Wei Cheng, Xiangge Tian, Xiaokui Huo, Yan Wang, Chengpeng Sun, Lei Feng, Jinshan Xing, Yulong Lan, Dongdong Sun, Qingjuan Hou, Baojing Zhang, Xiaochi Ma, Bo Zhang
BACKGROUND: Glioblastoma multiforme (GBM) is one of the most refractory and palindromic central nervous system (CNS) neoplasms, and current treatments have poor effects in GBM patients. Hence, the identification of novel therapeutic targets and the development of effective treatment strategies are essential. Alantolactone (ATL) has a wide range of pharmacological activities, and its anti-tumor effect is receiving increasing attention. However, the molecular mechanism underlying the anti-GBM activity of ATL remains poorly understood...
July 12, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28696296/multiplexed-rnai-therapy-against-brain-tumor-initiating-cells-via-lipopolymeric-nanoparticle-infusion-delays-glioblastoma-progression
#15
Dou Yu, Omar F Khan, Mario L Suvà, Biqin Dong, Wojciech K Panek, Ting Xiao, Meijing Wu, Yu Han, Atique U Ahmed, Irina V Balyasnikova, Hao F Zhang, Cheng Sun, Robert Langer, Daniel G Anderson, Maciej S Lesniak
Brain tumor-initiating cells (BTICs) have been identified as key contributors to therapy resistance, recurrence, and progression of diffuse gliomas, particularly glioblastoma (GBM). BTICs are elusive therapeutic targets that reside across the blood-brain barrier, underscoring the urgent need to develop novel therapeutic strategies. Additionally, intratumoral heterogeneity and adaptations to therapeutic pressure by BTICs impede the discovery of effective anti-BTIC therapies and limit the efficacy of individual gene targeting...
July 25, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28695794/the-natural-component-isolated-from-enterolobium-contortisiliquum-impairs-brain-tumors-and-affects-their-interactions-with-mesenchymal-stem-cells
#16
Camila Ramalho Bonturi, Helena Motaln, Mariana Cristina Cabral Silva, Bruno Ramos Salu, Marlon Vilela de Brito, Luciana de Andrade Luz Costa, Heron Fernandes Vieira Torquato, Natália Neto Dos Santos Nunes, Edgar Julian Paredes-Gamero, Tamara Lah Turnšek, Maria Luiza Vilela Oliva
Glioblastoma multiforme (GBM) is the most aggressive type of brain tumor with an overall patient survival of about 16 months. Thus, natural compounds with anti-cancer properties are gaining attention as possible alternatives for GBM treatment. Studies in various cancer models have shown the anti-cancer effects of the Enterolobium contortisiliquum Trypsin Inhibitor (EcTI). Here, we investigated the outcomes of EcTI on U87 cells, mesenchymal stem cells (MSC), and their direct cocultures (U87/MSC). MSC are present in tumor stroma and represent a potential drug delivery vehicle as the result of their tumor tropism...
July 11, 2017: Oncology Research
https://www.readbyqxmd.com/read/28687190/a-synthetic-bmp-2-mimicking-peptide-induces-glioblastoma-stem-cell-differentiation
#17
Elena Rampazzo, Monica Dettin, Francesca Maule, Alessandra Scabello, Luisa Calvanese, Gabriella D'Auria, Lucia Falcigno, Elena Porcù, Annj Zamuner, Alessandro Della Puppa, Daniele Boso, Giuseppe Basso, Luca Persano
BACKGROUND: Glioblastoma (GBM) is the most aggressive type of primary brain tumor, characterized by the intrinsic resistance to chemotherapy due to the presence of a highly aggressive Cancer Stem Cell (CSC) sub-population. In this context, Bone Morphogenetic Proteins (BMPs) have been demonstrated to induce CSC differentiation and to sensitize GBM cells to treatments. METHODS: The BMP-2 mimicking peptide, named GBMP1a, was synthesized on solid-phase by Fmoc chemistry...
September 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28674211/effects-of-soluble-cpe-on-glioma-cell-migration-are-associated-with-mtor-activation-and-enhanced-glucose-flux
#18
Elena I Ilina, Angela Armento, Leticia Garea Sanchez, Marina Reichlmeir, Yannick Braun, Cornelia Penski, David Capper, Felix Sahm, Lukas Jennewein, Patrick N Harter, Sven Zukunft, Ingrid Fleming, Dorothea Schulte, Francois Le Guerroué, Christian Behrends, Michael W Ronellenfitsch, Ulrike Naumann, Michel Mittelbronn
Carboxypeptidase E (CPE) has recently been described as a multifunctional protein that regulates proliferation, migration and survival in several tumor entities. In glioblastoma (GBM), the most malignant primary brain tumor, secreted CPE (sCPE) was shown to modulate tumor cell migration. In our current study, we aimed at clarifying the underlying molecular mechanisms regulating anti-migratory as well as novel metabolic effects of sCPE in GBM. Here we show that sCPE activates mTORC1 signaling in glioma cells detectable by phosphorylation of its downstream target RPS6...
June 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28668763/vascular-mimicry-a-novel-neovascularization-mechanism-driving-anti-angiogenic-therapy-aat-resistance-in-glioblastoma
#19
REVIEW
Kartik Angara, Thaiz F Borin, Ali S Arbab
Glioblastoma (GBM) is a hypervascular neoplasia of the central nervous system with an extremely high rate of mortality. Owing to its hypervascularity, anti-angiogenic therapies (AAT) have been used as an adjuvant to the traditional surgical resection, chemotherapy, and radiation. The benefits of AAT have been transient and the tumors were shown to relapse faster and demonstrated particularly high rates of AAT therapy resistance. Alternative neovascularization mechanisms were shown to be at work in these resilient tumors to counter the AAT therapy insult...
August 2017: Translational Oncology
https://www.readbyqxmd.com/read/28666273/macrophage-migration-inhibitory-factor-promotes-vasculogenic-mimicry-formation-induced-by-hypoxia-via-cxcr4-akt-emt-pathway-in-human-glioblastoma-cells
#20
Xing Guo, Shugang Xu, Xiao Gao, Jian Wang, Hao Xue, Zihang Chen, Jinsen Zhang, Xiaofan Guo, Mingyu Qian, Wei Qiu, Gang Li
Macrophage migration inhibitory factor (MIF) is over-expressed and secreted in various cancer cells in particular in response to hypoxia. Recent studies have shown that, under hypoxic conditions, glioblastoma (GBM) cells display the ability to drive blood-perfused vasculogenic mimicry (VM). The aim of this study was to investigate the underlying mechanism of MIF in the regulation of hypoxia-induced VM in GBM cells. By analyzing clinical specimens, we observed the co-localization of MIF, C-X-C motif chemokine receptor 4 (CXCR4) and VM in hypoxic regions of gliomas...
June 27, 2017: Oncotarget
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