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Immunology glioblastoma

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https://www.readbyqxmd.com/read/29643764/the-idh1-mutation-induced-oncometabolite-2-hydroxyglutarate-may-affect-dna-methylation-and-expression-of-pd-l1-in-gliomas
#1
Luyan Mu, Yu Long, Changlin Yang, Linchun Jin, Haipeng Tao, Haitao Ge, Yifan E Chang, Aida Karachi, Paul S Kubilis, Gabriel De Leon, Jiping Qi, Elias J Sayour, Duane A Mitchell, Zhiguo Lin, Jianping Huang
Background: Malignant gliomas are heterogeneous brain tumors with the potential for aggressive disease progression, as influenced by suppressive immunoediting. Given the success and enhanced potential of immune-checkpoint inhibitors in immunotherapy, we focused on the connections between genetic alterations affected by IDH1 mutations and immunological landscape changes and PDL-1 expression in gliomas. Methods: Paired surgically resected tumors from lower-grade gliomas (LGGs) and glioblastomas (GBM) were investigated, and a genetic analysis of patients' primary tumor samples culled from TCGA datasets was performed...
2018: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/29628799/clinical-and-immunological-correlates-of-long-term-survival-in-glioblastoma
#2
REVIEW
Bartosz Czapski, Szymon Baluszek, Christel Herold-Mende, Bozena Kaminska
Glioblastoma (GBM) is the most common and most aggressive type of primary brain tumour in adults. It represents 54% of all gliomas and 16% of all brain tumours (Ostrom et al. 2016). Despite surgery and treatment with radiotherapy plus an oral alkylating agent, temozolomide (TMZ), tumours invariably recur, and the patient survival is an average of ~14-16 months. In this review we summarise the current understanding of multiple factors that may affect survival of patients with GBMs. In particular, we discuss recent advancements in surgery and detection of genomic-based markers with prognostic values, such as IDH1/2 mutations, MGMT gene promoter methylation, and TERT gene promoter alterations...
March 2018: Contemporary Oncology Współczesna Onkologia
https://www.readbyqxmd.com/read/29593027/t-cell-dysfunction-in-glioblastoma-applying-a-new-framework
#3
Karolina I Woroniecka, Kristen E Rhodin, Pakawat Chongsathidkiet, Kristin A Keith, Peter E Fecci
A functional, replete T cell repertoire is an integral component to adequate immune surveillance and to the initiation and maintenance of productive anti-tumor immune responses. Glioblastoma (GBM), however, is particularly adept at sabotaging anti-tumor immunity, eliciting severe T cell dysfunction that is both qualitative and quantitative. Understanding and countering such dysfunction are among the keys to harnessing the otherwise stark potential of anti-cancer immune-based therapies. While T cell dysfunction in GBM is long described, newer immunologic frameworks now exist for re-classifying T cell deficits in a manner that better permits their study and reversal...
March 28, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29575677/vitamin-d-analogues-tacalcitol-and-calcipotriol-inhibit-proliferation-and-migration-of-t98g-human-glioblastoma-cells
#4
Ida Emanuelsson, Kjell Wikvall, Tomas Friman, Maria Norlin
The active form of vitamin D (1α,25-dihydroxyvitamin D) acts as a steroid hormone and binds to the vitamin D receptor (VDR). This receptor is expressed in most cell types including cells in the CNS. Vitamin D has several functions in the body including effects on brain development, neuroprotection and immunological regulation. It has been shown that vitamin D has anti-proliferative activities in different cancer cell lines. Tacalcitol and calcipotriol are synthetic analogues of 1α,25-dihydroxyvitamin D with reduced effect on calcium metabolism...
March 25, 2018: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/29492202/evaluating-vacquinol-1-in-rats-carrying-glioblastoma-models-rg2-and-ns1
#5
Jonatan Ahlstedt, Karolina Förnvik, Shaian Zolfaghari, Dongoh Kwak, Lars G J Hammarström, Patrik Ernfors, Leif G Salford, Henrietta Nittby Redebrandt
Glioblastoma multiforme (GBM) is the most common malignant primary brain tumor, and available experimental and routine therapies result in limited survival benefits. A vulnerability of GBM cells to catastrophic vacuolization and cell death, a process termed methuosis, induced by Vacquinol-1 (VQ-1) has been described earlier. In the present study, we investigate the efficacy of VQ-1 treatment in two syngeneic rat GBM models, RG2 and NS1. VQ-1 treatment affected growth of both RG2 and NS1 cells in vitro . Intracranially, significant reduction in RG2 tumor size was observed, although no effect was seen on overall survival...
February 2, 2018: Oncotarget
https://www.readbyqxmd.com/read/29484440/importance-of-immune-monitoring-approaches-and-the-use-of-immune-checkpoints-for-the-treatment-of-diffuse-intrinsic-pontine-glioma-from-bench-to-clinic-and-vice-versa-review
#6
Jorge Augusto Borin Scutti
On the basis of immunological results, it is not in doubt that the immune system is able to recognize and eliminate transformed cells. A plethora of studies have investigated the immune system of patients with cancer and how it is prone to immunosuppression, due in part to the decrease in lymphocyte proliferation and cytotoxic activity. The series of experiments published following the demonstration by Dr Allison's group of the potential effect of anti-cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) paved the way for a new perception in cancer immunotherapy: Immune checkpoints...
February 23, 2018: International Journal of Oncology
https://www.readbyqxmd.com/read/29387965/cell-biology-of-glioblastoma-multiforme-from-basic-science-to-diagnosis-and-treatment
#7
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
#8
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
#9
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
#10
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)...
April 2018: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/29213157/immunotherapy-and-gene-therapy-as-novel-treatments-for-cancer
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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...
December 6, 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
#17
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
#18
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
#19
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
#20
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
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