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Glioma T cell

Jaclyn J Renfrow, Michael H Soike, Waldemar Debinski, Shakti H Ramkissoon, Ryan T Mott, Mark B Frenkel, Jann N Sarkaria, Glenn J Lesser, Roy E Strowd
Hypoxia is an important contributor to aggressive behavior and resistance mechanisms in glioblastoma. Upregulation of hypoxia inducible transcription factors (HIFs) is the primary adaptive cellular response to a hypoxic environment. While HIF1α has been widely studied in cancer, HIF2α offers a potentially more specific and appealing target in glioblastoma given expression in glioma stem cells and not normal neural progenitors, activation in states of chronic hypoxia and expression that correlates with glioma patient survival...
August 9, 2018: Future Medicinal Chemistry
Eva Rainer, Hao Wang, Tatjana Traub-Weidinger, Georg Widhalm, Barbara Fueger, Jingling Chang, Zhaohui Zhu, Christine Marosi, Alexander Haug, Marcus Hacker, Shuren Li
PURPOSE: Recent studies have shown that tumor vascular endothelial cells and various tumor cells overexpress receptors for vascular endothelial growth factor (VEGF). The aim of this study was to investigate the prognostic value of [123 I]-VEGF scintigraphy in patients with histologically verified brain tumors. METHODS: 23 consecutive patients (9 women and 14 men aged 30-83 years, mean age 56.6 ± 14.4 years) with histopathologically-verified primary brain tumors were included in the study...
July 30, 2018: European Journal of Nuclear Medicine and Molecular Imaging
Mario Löhr, Benjamin Freitag, Antje Technau, Jürgen Krauss, Camelia-Maria Monoranu, Johannes Rachor, Manfred B Lutz, Carsten Hagemann, Almuth F Kessler, Thomas Linsenmann, Matthias Wölfl, Ralf-Ingo Ernestus, Sabrina Engelhardt, Götz Gelbrich, Paul G Schlegel, Matthias Eyrich
High-grade gliomas (HGG) exert systemic immunosuppression, which is of particular importance as immunotherapeutic strategies such as therapeutic vaccines are increasingly used to treat HGGs. In a first cohort of 61 HGG patients we evaluated a panel of 30 hematological and 34 plasma biomarkers. Then, we investigated in a second cohort of 11 relapsed HGG patients receiving immunomodulation with metronomic cyclophosphamide upfront to a DC-based vaccine whether immune abnormalities persisted and whether they hampered induction of IFNγ+ T-cell responses...
July 27, 2018: Cancer Immunology, Immunotherapy: CII
Carrie Bowman Dalley, Barbara Wroblewska, Barry B Wolfe, Jarda T Wroblewski
Glioma refers to malignant central nervous system tumors that have histological characteristics in common with glial cells. The most prevalent type, glioblastoma multiforme, is associated with a poor prognosis and few treatment options. Based on reports of aberrant expression of mGluR1 mRNA in glioma, evidence that melanoma growth is directly influenced by mGluR1, and characterization of β-arrestin dependent pro-survival signaling by this receptor, this study investigates the hypothesis that glioma cell lines aberrantly express mGluR1 and depend on mGluR1 mediated signaling to maintain viability and proliferation...
July 27, 2018: Journal of Pharmacology and Experimental Therapeutics
Tangi Roussel, Jens T Rosenberg, Samuel C Grant, Lucio Frydman
This study explores opportunities opened up by ultrahigh fields for in vivo saturation transfer brain magnetic resonance imaging experiments. Fast spin-echo images weighted by chemical exchange saturation transfer (CEST) effects were collected on Sprague-Dawley rats at 21.1 T, focusing on two neurological models. One involved a middle cerebral artery occlusion emulating ischemic stroke; the other involved xenografted glioma cells that were followed over the course of several days as they developed into brain tumors...
July 27, 2018: NMR in Biomedicine
Liu Zhenjiang, Martin Rao, Xiaohua Luo, Davide Valentini, Anna von Landenberg, Qingda Meng, Georges Sinclair, Nina Hoffmann, Julia Karbach, Hans-Michael Altmannsberger, Elke Jäger, Inti Harvey Peredo, Ernest Dodoo, Markus Maeurer
PURPOSE: We investigated serum cytokine and T-cell responses directed against tumour-associated antigens (TAAs) in association with survival of patients with glioblastoma multiforme (GBM). PATIENTS AND METHODS: Peripheral blood from 205 treatment-naïve patients with glioma (GBM = 145; non-GBM = 60) was obtained on the day of surgery to measure (i) circulating T-cells reacting to viral antigens and TAAs, in the presence or absence of cytokine conditioning with IL-2/IL-15/IL-21 or IL-2/IL-7, and (ii) serum cytokine levels (IL-4, IL-5, IL-6, TNF-α, IFN-γ and IL-17A)...
July 2018: EBioMedicine
Nasim Rahmani Kukia, Reza Alipanah-Moghadam, Nowruz Delirezh, Mohammad Mazani
Background: Immunotherapy is one promising therapeutic strategy against glioma, an aggressive form of brain cancer. Previous studies have demonstrated that multiple tumor antigens exist and can be used to induce tumor specific T cell responses. Furthermore, recently it was shown that TLR4-primed mesenchymal stem cells (MSCs), also known as MSC1, mostly elaborate pro-inflammatory mediators. Compared to MSCs, MSC-derived microvesicles (MVs) have advantageous properties that present them as stable, long lasting effectors with no risk of immune rejection...
July 27, 2018: Asian Pacific Journal of Cancer Prevention: APJCP
Theresa Barberi, Allison Martin, Rahul Suresh, David J Barakat, Sarah Harris-Bookman, Charles G Drake, Michael Lim, Alan D Friedman
High-grade gliomas harbor abundant myeloid cells that suppress anti-tumor immunity and support tumor growth. Targeting transcription factors, such as NF-κB p50, that mediate suppressive myeloid M2 polarization may prove therapeutic. GL261-Luc glioblastoma cells were inoculated into wild-type and p50-/- mice, followed by analysis of tumor growth, survival, tumor myeloid cells, and T cells. The absence of host p50 slows tumor growth and enables regression in 30% of recipients, leading to prolonged survival. Tumors developing in p50-/- mice possess a greater concentration of tumor-infiltrating myeloid cells (TIMs) than those in wild-type mice...
July 21, 2018: Cancer Immunology, Immunotherapy: CII
(no author information available yet)
IDH1 mutation-derived R-2-HG blocks T-cell activation and proliferation in gliomas.
July 20, 2018: Cancer Discovery
Zhiliang Wang, Zheng Wang, Chuanbao Zhang, Xing Liu, Guanzhang Li, Shuai Liu, Lihua Sun, Jingshan Liang, Huimin Hu, Yanwei Liu, Wei Zhang, Tao Jiang
Glioma is the most common malignant tumor that primarily originated from brain tissue. Immune checkpoints have been increasingly emphasized as targets for treating malignant tumors. B7-H3, has been identified as an immune checkpoint which shows potential values for targeting therapies. We set out to characterize the expression pattern and biological function of B7-H3 in brain gliomas via high-throughput data obtained from CGGA and TCGA projects. B7-H3 was upregulated in higher grade gliomas than that in lower grade gliomas in both CGGA and TCGA datasets...
July 20, 2018: Cancer Science
Julius W Kim, J Robert Kane, Wojciech K Panek, Jacob S Young, Aida Rashidi, Dou Yu, Deepak Kanojia, Tanwir Hasan, Jason Miska, Miguel A Gómez-Lim, Ilya V Ulasov, Irina V Balyasnikova, Atique U Ahmed, Derek A Wainwright, Maciej S Lesniak
Antitumor immunotherapeutic strategies represent an especially promising set of approaches with rapid translational potential considering the dismal clinical context of high-grade gliomas. Dendritic cells (DCs) are the body's most professional antigen-presenting cells, able to recruit and activate T cells to stimulate an adaptive immune response. In this regard, specific loading of tumor-specific antigen onto dendritic cells potentially represents one of the most advanced strategies to achieve effective antitumor immunization...
July 19, 2018: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
Yoshiko Okita, Tomoko Shofuda, Daisuke Kanematsu, Ema Yoshioka, Yoshinori Kodama, Masayuki Mano, Manabu Kinoshita, Masahiro Nonaka, Shin Nakajima, Toshiyuki Fujinaka, Yonehiro Kanemura
Gliomas are genetically and histopathologically heterogeneous. Intratumoral heterogeneity in the MGMT promoter methylation status is an important clinical biomarker of glioblastoma. A higher uptake of 11 C-methionine in positron-emission tomography (PET) reportedly reflects increased MGMT promoter methylation; however, non-stereotactic comparison of MGMT methylation and 11 C-methionine PET images may not be accurate. The present study examined the correlation between 11 C-methionine uptake and MGMT promoter methylation in non-enhancing gliomas using stereotactic image-based histological analysis...
August 2018: Oncology Letters
Lingjun Zhang, Mia Sorensen, Bjarne W Kristensen, Guido Reifenberger, Thomas M McIntyre, Feng Lin
PURPOSE: Somatic mutations in the isocitrate dehydrogenase (IDH)-1 and -2 genes are remarkably penetrant in diffuse gliomas. These highly effective gain-of-function mutations enable mutant IDH to efficiently metabolize isocitrate to D-2-hydroxyglutarate (D 2-HG) that accumulates to high concentrations within the tumor microenvironment. D 2-HG is an intracellular effector that promotes tumor growth through widespread epigenetic changes in IDH mutant tumor cells, but its potential role as an intercellular immune regulator remains understudied...
July 13, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Enrique R Perez, Olena Bracho, Liliana Ein, Mikhaylo Szczupak, Paula V Monje, Cristina Fernandez-Valle, Abdulaziz Alshaiji, Michael Ivan, Jacques Morcos, Xue-Zhong Liu, Michael Hoffer, Adrien Eshraghi, Simon Angeli, Fred Telischi, Christine T Dinh
HYPOTHESIS: Merlin-deficient Schwann cells (MD-SC) and primary human vestibular schwannoma (VS) cells exhibit selective uptake of sodium-fluorescein (SF), allowing for fluorescent detection and improved visualization of tumor cells, when compared with Schwann cells (SC). BACKGROUND: SF is a fluorescent compound used for fluorescence-guided resection of gliomas. The utility of SF for VS surgery has not been assessed. METHODS: Mouse MD-SCs and rat SCs were cultured on 96-well plates at different cell densities and treated with SF at several drug concentrations and durations...
July 9, 2018: Otology & Neurotology
Krissie Lenting, Mohammed Khurshed, Tom H Peeters, Corina N A M van den Heuvel, Sanne A M van Lith, Tessa de Bitter, Wiljan Hendriks, Paul N Span, Remco J Molenaar, Dennis Botman, Kiek Verrijp, Arend Heerschap, Mark Ter Laan, Benno Kusters, Anne van Ewijk, Martijn A Huynen, Cornelis J F van Noorden, William P J Leenders
Diffuse gliomas often carry point mutations in isocitrate dehydrogenase ( IDH1mut ), resulting in metabolic stress. Although IDHmut gliomas are difficult to culture in vitro, they thrive in the brain via diffuse infiltration, suggesting brain-specific tumor-stroma interactions that can compensate for IDH-1 deficits. To elucidate the metabolic adjustments in clinical IDHmut gliomas that contribute to their malignancy, we applied a recently developed method of targeted quantitative RNA next-generation sequencing to 66 clinical gliomas and relevant orthotopic glioma xenografts, with and without the endogenous IDH-1R132H mutation...
July 12, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Ross W Walton, Michael C Brown, Matthew T Sacco, Matthias Gromeier
We are pursuing cancer immunotherapy with neuro-attenuated recombinant poliovirus, PVSRIPO. PVSRIPO is the live attenuated type 1 (Sabin) poliovirus vaccine carrying a heterologous internal ribosomal entry site (IRES) of human rhinovirus type 2 (HRV2). Intratumoral infusion of PVSRIPO is showing promise in the therapy of recurrent WHO grade IV malignant glioma (glioblastoma), a notoriously treatment-refractory cancer with dismal prognosis. PVSRIPO exhibits profound cytotoxicity in infected neoplastic cells expressing the poliovirus receptor CD155...
July 11, 2018: Journal of Virology
Shanyue Sun, Guangying Du, Jiang Xue, Jinbo Ma, Minmin Ge, Hongbo Wang, Jingwei Tian
Indoleamine 2,3-dioxygenase (IDO), which is highly expressed in human glioblastoma and involved in tumor immune escape and resistance to chemotherapy, is clinically correlated with tumor progression and poor clinical outcomes, and is a promising therapeutic target for glioblastoma. IDO inhibitors are marginally efficacious as single-agents; therefore, combination with other therapies holds promise for cancer therapy. The aim of this study was to investigate the anti-tumor effects and mechanisms of the IDO inhibitor PCC0208009 in combination with temozolomide...
January 2018: International Journal of Immunopathology and Pharmacology
Eric T Wong, Edwin Lok, Kenneth D Swanson
Alternating electric fields of intermediate frequencies, also known as Tumor Treating Fields (TTFields or TTF) is a novel anticancer treatment modality that disrupts tumor cell mitosis at the metaphase-anaphase transition, leading to mitotic catastrophe, aberrant mitotic exit, and/or cell death. It is realized through alteration of the cytokinetic cleavage furrow by interference of proteins possessing large dipole moments, like septin heterotrimer complex and α/β-tubulin, and that results in disordered membrane contraction and failed cytokinesis...
2018: Progress in Neurological Surgery
Lukas Bunse, Stefan Pusch, Theresa Bunse, Felix Sahm, Khwab Sanghvi, Mirco Friedrich, Dalia Alansary, Jana K Sonner, Edward Green, Katrin Deumelandt, Michael Kilian, Cyril Neftel, Stefanie Uhlig, Tobias Kessler, Anna von Landenberg, Anna S Berghoff, Kelly Marsh, Mya Steadman, Dongwei Zhu, Brandon Nicolay, Benedikt Wiestler, Michael O Breckwoldt, Ruslan Al-Ali, Simone Karcher-Bausch, Matthias Bozza, Iris Oezen, Magdalena Kramer, Jochen Meyer, Antje Habel, Jessica Eisel, Gernot Poschet, Michael Weller, Matthias Preusser, Minou Nadji-Ohl, Niklas Thon, Michael C Burger, Patrick N Harter, Miriam Ratliff, Richard Harbottle, Axel Benner, Daniel Schrimpf, Jürgen Okun, Christel Herold-Mende, Sevin Turcan, Stefan Kaulfuss, Holger Hess-Stumpp, Karen Bieback, Daniel P Cahill, Karl H Plate, Daniel Hänggi, Marion Dorsch, Mario L Suvà, Barbara A Niemeyer, Andreas von Deimling, Wolfgang Wick, Michael Platten
The oncometabolite (R)-2-hydroxyglutarate (R-2-HG) produced by isocitrate dehydrogenase (IDH) mutations promotes gliomagenesis via DNA and histone methylation. Here, we identify an additional activity of R-2-HG: tumor cell-derived R-2-HG is taken up by T cells where it induces a perturbation of nuclear factor of activated T cells transcriptional activity and polyamine biosynthesis, resulting in suppression of T cell activity. IDH1-mutant gliomas display reduced T cell abundance and altered calcium signaling...
July 9, 2018: Nature Medicine
Ayguen Sahin, Carlos Sanchez, Szofia Bullain, Peter Waterman, Ralph Weissleder, Bob S Carter
Glioblastoma multiforme (GBM) is the most aggressive and deadly form of adult brain cancer. Despite of many attempts to identify potential therapies for this disease, including promising cancer immunotherapy approaches, it remains incurable. To address the need of improved persistence, expansion, and optimal antitumor activity of T-cells in the glioma milieu, we have developed an EGFRvIII-specific third generation (G3-EGFRvIII) chimeric antigen receptor (CAR) that expresses both co-stimulatory factors CD28 and OX40 (MR1-CD8TM-CD28-OX40-CD3ζ)...
2018: PloS One
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