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Immunology glioblastoma

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https://www.readbyqxmd.com/read/29387965/cell-biology-of-glioblastoma-multiforme-from-basic-science-to-diagnosis-and-treatment
#1
George S Stoyanov, Deyan Dzhenkov, Peter Ghenev, Bogomil Iliev, Yavor Enchev, Anton B Tonchev
First described in the 1800s, glioblastoma multiforme (GBM), a class IV neoplasm with astrocytic differentiation, as per the revised 2016 World Health Organization classification of tumors of the central nervous system (CNS) is the most common malignant tumor of the CNS. GBM has an extremely wide set of alterations, both genetic and epigenetic, which yield a great number of mutation subgroups, some of which have an established role in independent patient survival and treatment response. All of those components not only represent a closed cycle but are also relevant to the tumor biological behavior and resistance to treatment as they form the pathobiological behavior and clinical course...
January 31, 2018: Medical Oncology
https://www.readbyqxmd.com/read/29383986/neuroprotective-and-tumoricidal-activities-of-cardiac-glycosides-could-oleandrin-be-a-new-weapon-against-stroke-and-glioblastoma
#2
İlhan Elmaci, Ebru Emekli Alturfan, Salih Cengiz, Aysel Ozpinar, Meric A Altinoz
Cardiac glycosides induce a strong immunological cancer cell cytotoxicity, in which the released intracellular components of dying tumor cells (eg. calreticulin, HMGB1 and ATP) stimulate immunity and help in eradicating cancer. Among the cardiac glycosides, oleandrin is an inhibitor of P-glycoprotein expression and exerts excellent penetration through the blood-brain barrier which also harbours neuroprotective and anti-glioma efficacies. Cardiac glycosides also exert neuroprotective activities, one explanation for such an action is the metabolic arrest as a defense strategy against hypoxia...
January 31, 2018: International Journal of Neuroscience
https://www.readbyqxmd.com/read/29356965/nkg2d-ligands-in-glioma-stem-like-cells-expression-in-situ-and-in-vitro
#3
Charlotte Flüh, Guranda Chitadze, Vivian Adamski, Kirsten Hattermann, Michael Synowitz, Dieter Kabelitz, Janka Held-Feindt
Glioblastoma multiforme (GBM) is a highly malignant brain tumor. Tumor stem cells have a major influence on tumor malignancy, and immunological escape mechanisms, involving the Natural Killer Group 2, member D (NKG2D) receptor-ligand-system, are key elements in tumor immuno-surveillance. We analyzed the expression profile and localization of NKG2D ligands (NKG2DL) and embryonic and neural stem cell markers in solid human GBM and stem-like cells isolated from glioma cell lines by qRT-PCR and immunohistochemistry, including quantitative analysis...
January 22, 2018: Histochemistry and Cell Biology
https://www.readbyqxmd.com/read/29302887/analysis-of-immunobiologic-markers-in-primary-and-recurrent-glioblastoma
#4
Maryam Rahman, Jesse Kresak, Changlin Yang, Jianping Huang, Wesley Hiser, Paul Kubilis, Duane Mitchell
Glioblastoma (GBM) generates a varied immune response and understanding the immune microenvironment may lead to novel immunotherapy treatments modalities. The goal of this study was to evaluate the expression of immunologic markers of potential clinical significance in primary versus recurrent GBM and assess the relationship between these markers and molecular characteristics of GBM. Human GBM samples were evaluated and analyzed with immunohistochemistry for multiple immunobiologic markers (CD3, CD8, FoxP3, CD68, CD163, PD1, PDL1, CTLA4, CD70)...
January 4, 2018: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/29213157/immunotherapy-and-gene-therapy-as-novel-treatments-for-cancer
#5
REVIEW
Martha Montserrat Rangel-Sosa, Estuardo Aguilar-Córdova, Augusto Rojas-Martínez
The immune system interacts closely with tumors during the disease development and progression to metastasis. The complex communication between the immune system and the tumor cells can prevent or promote tumor growth. New therapeutic approaches harnessing protective immunological mechanisms have recently shown very promising results. This is performed by blocking inhibitory signals or by activating immunological effector cells directly. Immune checkpoint blockade with monoclonal antibodies directed against the inhibitory immune receptors CTLA-4 and PD-1 has emerged as a successful treatment approach for patients with advanced melanoma...
September 30, 2017: Colombia Médica: CM
https://www.readbyqxmd.com/read/29147621/in-depth-immunophenotyping-of-patients-with-glioblastoma-multiforme-impact-of-steroid-treatment
#6
Guranda Chitadze, Charlotte Flüh, Elgar Susanne Quabius, Sandra Freitag-Wolf, Christian Peters, Marcus Lettau, Jaydeep Bhat, Daniela Wesch, Hans-Heinrich Oberg, Stefanie Luecke, Ottmar Janssen, Michael Synowitz, Janka Held-Feindt, Dieter Kabelitz
Despite aggressive treatment regimens based on surgery and radiochemotherapy, the prognosis of patients with grade IV glioblastoma multiforme (GBM) remains extremely poor, calling for alternative options such as immunotherapy. Immunological mechanisms including the Natural Killer Group 2 member D (NKG2D) receptor-ligand system play an important role in tumor immune surveillance and targeting the NKG2D system might be beneficial. However, before considering any kind of immunotherapy, a precise characterization of the immune system is important, particularly in GBM patients where conventional therapies with impact on the immune system are frequently co-administered...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/29113296/mesothelin-as-a-novel-biomarker-and-immunotherapeutic-target-in-human-glioblastoma
#7
Zhenjiang Liu, Martin Rao, Thomas Poiret, Silvia Nava, Qingda Meng, Anna von Landenberg, Jiri Bartek, Shanshan Xie, Georges Sinclair, Inti Peredo, Ernest Dodoo, Markus Maeurer
Glioblastoma multiforme (GBM) presents the most malignant form of glioma, with a 5-year survival rate below 3% despite standard therapy. Novel immune-based therapies in improving treatment outcomes in GBM are therefore warranted. Several molecularly defined targets have been identified mediating anti-GBM cellular immune responses. Mesothelin is a tumor-associated antigen (TAA) which is expressed in several solid tumors with different histology. Here, we report the immunological significance of mesothelin in human malignant glioma...
October 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/29091775/single-cell-rna-seq-analysis-of-infiltrating-neoplastic-cells-at-the-migrating-front-of-human-glioblastoma
#8
Spyros Darmanis, Steven A Sloan, Derek Croote, Marco Mignardi, Sophia Chernikova, Peyman Samghababi, Ye Zhang, Norma Neff, Mark Kowarsky, Christine Caneda, Gordon Li, Steven D Chang, Ian David Connolly, Yingmei Li, Ben A Barres, Melanie Hayden Gephart, Stephen R Quake
Glioblastoma (GBM) is the most common primary brain cancer in adults and is notoriously difficult to treat because of its diffuse nature. We performed single-cell RNA sequencing (RNA-seq) on 3,589 cells in a cohort of four patients. We obtained cells from the tumor core as well as surrounding peripheral tissue. Our analysis revealed cellular variation in the tumor's genome and transcriptome. We were also able to identify infiltrating neoplastic cells in regions peripheral to the core lesions. Despite the existence of significant heterogeneity among neoplastic cells, we found that infiltrating GBM cells share a consistent gene signature between patients, suggesting a common mechanism of infiltration...
October 31, 2017: Cell Reports
https://www.readbyqxmd.com/read/29066810/immunotherapy-with-subcutaneous-immunogenic-autologous-tumor-lysate-increases-murine-glioblastoma-survival
#9
Jochen Belmans, Matthias Van Woensel, Brecht Creyns, Joost Dejaegher, Dominique M Bullens, Stefaan W Van Gool
Immunotherapeutic strategies for glioblastoma, the most frequent malignant primary brain tumor, aim to improve its disastrous consequences. On top of the standard treatment, one strategy uses T cell activation by autologous dendritic cells (DC) ex vivo loaded with tumor lysate to attack remaining cancer cells. Wondering whether 'targeting' in vivo DCs could replace these ex vivo ones, immunogenic autologous tumor lysate was used to treat glioma-inoculated mice in the absence of ex vivo loaded DCs. Potential immune mechanisms were studied in two orthotopic, immunocompetent murine glioma models...
October 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28967558/oncolytic-h-1-parvovirus-shows-safety-and-signs-of-immunogenic-activity-in-a-first-phase-i-iia-glioblastoma-trial
#10
Karsten Geletneky, Jacek Hajda, Assia L Angelova, Barbara Leuchs, David Capper, Andreas J Bartsch, Jan-Oliver Neumann, Tilman Schöning, Johannes Hüsing, Birgit Beelte, Irina Kiprianova, Mandy Roscher, Rauf Bhat, Andreas von Deimling, Wolfgang Brück, Alexandra Just, Veronika Frehtman, Stephanie Löbhard, Elena Terletskaia-Ladwig, Jeremy Fry, Karin Jochims, Volker Daniel, Ottheinz Krebs, Michael Dahm, Bernard Huber, Andreas Unterberg, Jean Rommelaere
Oncolytic virotherapy may be a means of improving the dismal prognosis of malignant brain tumors. The rat H-1 parvovirus (H-1PV) suppresses tumors in preclinical glioma models, through both direct oncolysis and stimulation of anticancer immune responses. This was the basis of ParvOryx01, the first phase I/IIa clinical trial of an oncolytic parvovirus in recurrent glioblastoma patients. H-1PV (escalating dose) was administered via intratumoral or intravenous injection. Tumors were resected 9 days after treatment, and virus was re-administered around the resection cavity...
August 24, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28948650/vegf-as-a-modulator-of-the-innate-immune-response-in-glioblastoma
#11
Kati Turkowski, Susan Brandenburg, Annett Mueller, Irina Kremenetskaia, Alexander D Bungert, Anne Blank, Matthäus Felsenstein, Peter Vajkoczy
VEGF is an important factor in tumor vascularization and used as target for anti-angiogenic treatment strategies in glioma. In this study, we demonstrate for the first time that VEGF is a modulator of the innate immune response with suppressive effects on the immunologic and pro-angiogenic function of microglia/macrophages in a glioblastoma rodent model. High level of VEGF led to threefold enlarged tumor volumes and a pronounced remodeling of the vascular structure along with a reduced infiltration of microglia/macrophages by approximately 50%...
January 2018: Glia
https://www.readbyqxmd.com/read/28791656/egfr-as-a-target-for-glioblastoma-treatment-an-unfulfilled-promise
#12
Manfred Westphal, Cecile L Maire, Katrin Lamszus
The receptor for epidermal growth factor (EGFR) is a prime target for cancer therapy across a broad variety of tumor types. As it is a tyrosine kinase, small molecule tyrosine kinase inhibitors (TKIs) targeting signal transduction, as well as monoclonal antibodies against the EGFR, have been investigated as anti-tumor agents. However, despite the long-known enigmatic EGFR gene amplification and protein overexpression in glioblastoma, the most aggressive intrinsic human brain tumor, the potential of EGFR as a target for this tumor type has been unfulfilled...
September 2017: CNS Drugs
https://www.readbyqxmd.com/read/28716484/the-anti-tumor-activity-of-the-stat3-inhibitor-stx-0119-occurs-via-promotion-of-tumor-infiltrating-lymphocyte-accumulation-in-temozolomide-resistant-glioblastoma-cell-line
#13
Yasuto Akiyama, Chizu Nonomura, Tadashi Ashizawa, Akira Iizuka, Ryota Kondou, Haruo Miyata, Takashi Sugino, Koichi Mitsuya, Nakamasa Hayashi, Yoko Nakasu, Akira Asai, Mamoru Ito, Yoshio Kiyohara, Ken Yamaguchi
STAT3 is considered to be a key molecule to mediating tumor-induced immunosuppression in various manners at tumor sites, by acting through immune-regulatory cytokines derived from the tumor cells. Specific anti-STAT3 inhibitors have been developed using nude mouse models transplanted with human tumor cells. However, mouse systems cannot accurately represent the human immune response induced by STAT3 inhibitors, and more humanized therapeutic model based on human immune cells and tumors are needed. In the present study, an immune-deficient NOG mouse with the deletion of both MHC-class I and class II genes, an MHC-double knockout mouse (dKO-NOG), was developed and used to establish humanized immunotherapeutic model...
July 15, 2017: Immunology Letters
https://www.readbyqxmd.com/read/28697342/tumor-evolution-of-glioma-intrinsic-gene-expression-subtypes-associates-with-immunological-changes-in-the-microenvironment
#14
Qianghu Wang, Baoli Hu, Xin Hu, Hoon Kim, Massimo Squatrito, Lisa Scarpace, Ana C deCarvalho, Sali Lyu, Pengping Li, Yan Li, Floris Barthel, Hee Jin Cho, Yu-Hsi Lin, Nikunj Satani, Emmanuel Martinez-Ledesma, Siyuan Zheng, Edward Chang, Charles-Etienne Gabriel Sauvé, Adriana Olar, Zheng D Lan, Gaetano Finocchiaro, Joanna J Phillips, Mitchel S Berger, Konrad R Gabrusiewicz, Guocan Wang, Eskil Eskilsson, Jian Hu, Tom Mikkelsen, Ronald A DePinho, Florian Muller, Amy B Heimberger, Erik P Sulman, Do-Hyun Nam, Roel G W Verhaak
We leveraged IDH wild-type glioblastomas, derivative neurospheres, and single-cell gene expression profiles to define three tumor-intrinsic transcriptional subtypes designated as proneural, mesenchymal, and classical. Transcriptomic subtype multiplicity correlated with increased intratumoral heterogeneity and presence of tumor microenvironment. In silico cell sorting identified macrophages/microglia, CD4+ T lymphocytes, and neutrophils in the glioma microenvironment. NF1 deficiency resulted in increased tumor-associated macrophages/microglia infiltration...
July 10, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28646347/alendronate-treatment-induces-il-1b-expression-and-apoptosis-in-glioblastoma-cell-line
#15
Paola Maura Tricarico, Angeladine Epate, Fulvio Celsi, Sergio Crovella
Alendronate (ALD), one among the nitrogen-containing bisphosphonates (NBPs), is currently used for the treatment of many pathological conditions. Unfortunately, although generally tolerated, NBPs treatment has been associated with central nervous system (CNS) adverse outcomes, such as amnesia, hallucinations and visual disturbances. So, we analyzed the effect of ALD treatment in glial cells, the main sources of cholesterol for neurons and principal cells involved in the immunological defense of the brain. We treated a glial cell line (U87-MG) with increasing doses of ALD (0...
June 23, 2017: Inflammopharmacology
https://www.readbyqxmd.com/read/28531337/correlation-of-immune-phenotype-with-idh-mutation-in-diffuse-glioma
#16
Anna Sophie Berghoff, Barbara Kiesel, Georg Widhalm, Dorothee Wilhelm, Orsolya Rajky, Sebastian Kurscheid, Philip Kresl, Adelheid Wöhrer, Christine Marosi, Monika E Hegi, Matthias Preusser
Background: Tumor infiltrating lymphocytes (TILs) and programmed death ligand 1 (PD-L1) are targets of immune checkpoint inhibitors. Methods: Forty-three World Health Organization (WHO) grade II/III gliomas (39 IDH-mutant [mut], 4 IDH-wildtype [wt]) and 14 IDH-mut glioblastomas (GBM) were analyzed for TIL (CD3+; PD1+) infiltration and PD-L1 expression. Results were compared with the data of a previously published series of 117 IDH-wt glioblastomas. PD-L1 gene expression levels were evaluated in 677 diffuse gliomas grades II-IV from The Cancer Genome Atlas (TCGA) database...
October 19, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/28476689/pax6-interacts-with-iba1-and-shows-age-associated-alterations-in-brain-of-aging-mice
#17
Shashank Kumar Maurya, Rajnikant Mishra
The Pax6, a transcriptional regulator and multifunctional protein, has been found critical for neurogenesis, neuro-degeneration, mental retardation, neuroendocrine tumors, glioblastoma and astrocytomas. The age-associated alteration in the expression of Pax6 in neuron and glia has also been observed in the immunologically privileged brain. Therefore, it is presumed that Pax6 may modulate brain immunity by activation of microglia either directly interacting with genes or proteins of microglia or indirectly though inflammation associated with neurodegeneration...
May 3, 2017: Journal of Chemical Neuroanatomy
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/28025034/ccl2-ccr2-signaling-pathway-in-glioblastoma-multiforme
#19
REVIEW
Alireza Vakilian, Hossein Khorramdelazad, Parisa Heidari, Zahra Sheikh Rezaei, Gholamhossein Hassanshahi
Glioblastoma multiform (GBM) is described as one of the most frequent primary brain tumors. These types of malignancies constitute only 15% of all primary brain tumors. Despite, extensive developments on effective therapeutic methods during the 20th century as well as the first decade of the present century (21st), the median survival rate for patients suffering from GBM is only approximately 15 months, even in response to multi-modal therapy. numerous types of reticuloendothelial system cells such as macrophages and microglial cells occupied within both GBM and also normal surrounding tissues...
February 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28003545/anti-pd-1-antitumor-immunity-is-enhanced-by-local-and-abrogated-by-systemic-chemotherapy-in-gbm
#20
Dimitrios Mathios, Jennifer E Kim, Antonella Mangraviti, Jillian Phallen, Chul-Kee Park, Christopher M Jackson, Tomas Garzon-Muvdi, Eileen Kim, Debebe Theodros, Magdalena Polanczyk, Allison M Martin, Ian Suk, Xiaobu Ye, Betty Tyler, Chetan Bettegowda, Henry Brem, Drew M Pardoll, Michael Lim
The immunosuppressive effects of chemotherapy present a challenge for designing effective cancer immunotherapy strategies. We hypothesized that although systemic chemotherapy (SC) exhibits negative immunologic effects, local chemotherapy (LC) can potentiate an antitumor immune response. We show that LC combined with anti-programmed cell death protein 1 (PD-1) facilitates an antitumor immune response and improves survival (P < 0.001) in glioblastoma. LC-treated mice had increased infiltration of tumor-associated dendritic cells and clonal expansion of antigen-specific T effector cells...
December 21, 2016: Science Translational Medicine
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