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Glioma T cell

X T Li, J C Li, M Feng, Y X Zhou, Z W Du
Glioma is the most common sub-type of brain tumor. Due to the presence of stem-like cells, it is characterized by poor prognosis, aggressive ability and high post-surgical recurrence rates. Hence, there is critical need to identify molecular mechanisms of glioma stem-like cells. We found a novel lncRNA in the ZNF281 gene and named it lncRNA-ZNF281. We detected the expression of lncRNA-ZNF281 in glioma stem-like cells (U251s), the glioma cell line (U251) and also in normal brain tissue. The expression of lncRNA-ZNF281 was lower in glioma stem-like cells (U251s) and this indicates that lncRNA-ZNF281 can regulate the self-renewal capacity of glioma stem-like cells and stem cell marker expression...
September 4, 2018: Neoplasma
Tom B Davidson, Alexander H Lee, Melody Hsu, Shaina Sedighim, Joey Orpilla, Janet Treger, Maximilian Mastall, Saskia Roesch, Carmen Rapp, Mildred Galvez, Aaron Y Mochizuki, Joseph P Antonios, Alejandro J Garcia, Nikesh Kotecha, Nicholas L Bayless, David A Nathanson, Anthony C Wang, Richard G Everson, William H Yong, Timothy F Cloughesy, Linda M Liau, Christel C Herold-Mende, Robert M Prins
PURPOSE: Glioblastoma (GBM) is the most common primary malignant tumor in the central nervous system. Our recent pre-clinical work has suggested that PD-1/PD-L1 plays an important immunoregulatory role to limit effective anti-tumor T cell responses induced by active immunotherapy. However, little is known about the functional role that PD-1 plays on human T lymphocytes in malignant glioma patients. EXPERIMENTAL DESIGN: In this study, we examined the immune landscape and function of PD-1 expression on T cells from the tumor and peripheral blood in malignant glioma patients...
November 29, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Ali Neshasteh-Riz, Nazila Eyvazzadeh, Aram Rostami, Elmira Azzizolahi
Purpose: Glioblastoma multiform (GBM) is one of the most common brain tumors. Surgery, radiation therapy, hyperthermia, and chemotherapy are the most common treatments for brain tumors such as GBM. This study investigated the cytogenetic damage caused by hyperthermia, radiation (6 MV-X-rays), and topotecan in glioma spheroids, simultaneously and separately. Materials and Methods: Human glioblastoma cell line was cultured to form spheroids 350 μm in diameter that were arranged in eight groups and coded as follows: control, T: topotecan, H: hyperthermia, T + H: topotecan + hypertermia, X 1-10: X-ray with 1-10 fraction irradiation, H + X (1-10): hypertermia + X-ray with 1-10 fraction irradiation, T + X (1-10): topotecan + X-ray with 1-10 fraction irradiation, and H + T + X (1-10): hypertermia + topotecan + X-ray with 1-10 fraction irradiation...
October 2018: Journal of Cancer Research and Therapeutics
Elles J T M van der Louw, Roel E Reddingius, Joanne F Olieman, Rinze F Neuteboom, Coriene E Catsman-Berrevoets
BACKGROUND: The mean overall survival rate of children with diffuse intrinsic pontine glioma (DIPG) is 9-11 months, with current standard treatment with fractionated radiotherapy and adjuvant chemotherapy. So far, novel therapeutic strategies have not yet resulted in significantly better survival. The main source of energy for glioblastoma cells is glucose. Therefore, metabolic alterations induced by the use of the extremely carbohydrate-restricted ketogenic diet (KD) as adjuvant therapy are subject of interest in cancer research...
November 28, 2018: Pediatric Blood & Cancer
Y Y Li, X H Chen, T Sun, Y Hu, Y H Zhou, Y X Zhou
Objective: To investigate the roles and anti-cancer mechanism of artificially synthesized EGF-containing fibulin-like extracellular matrix protein (EFEMP1) derived tumor suppressor ZR30 protein in glioma (GBM). Methods: ZR30 protein were in vitro expressed using a wheat germ cell-free system. GBM cell lines (U251, U251NS, and U87) were cultured for 2-3 days in the presence or absence of ZR30 treatment. MMP-2 level was detected by gelatin zymography assay, moreover, the expression of EGFR, Notch-1 and p-Akt/Akt levels were determined by western blot...
November 23, 2018: Zhonghua Zhong Liu za Zhi [Chinese Journal of Oncology]
Wojciech K Panek, Katarzyna C Pituch, Jason Miska, Julius W Kim, Aida Rashidi, Deepak Kanojia, Aurora Lopez-Rosas, Yu Han, Dou Yu, Catalina Lee Chang, J Robert Kane, Peng Zhang, Alex Cordero, Maciej S Lesniak
The immunosuppressive microenvironment is one of the major factors promoting the growth of glioblastoma multiforme (GBM). Infiltration of CD4+ CD25+ Foxp3+ regulatory T cells (Tregs) into the tumor microenvironment plays a significant role in the suppression of the anti-tumor immunity and portends a dismal prognosis for patients. Glioma-mediated secretion of chemo-attractant C-C motif ligand 2 and 22 (CCL2/22) has previously been shown by our group to promote Treg migration in vitro. In this study, we show that a local implantation of platelet-rich fibrin patch (PRF-P) into the brain of GL261 glioma-bearing mice prolonged the survival of affected animals by 42...
November 20, 2018: Molecular Neurobiology
Kathryn M Kingsmore, Andrea Vaccari, Daniel Abler, Sophia X Cui, Frederick H Epstein, Russell C Rockne, Scott T Acton, Jennifer M Munson
Glioblastoma (GBM), a highly aggressive form of brain tumor, is a disease marked by extensive invasion into the surrounding brain. Interstitial fluid flow (IFF), or the movement of fluid within the spaces between cells, has been linked to increased invasion of GBM cells. Better characterization of IFF could elucidate underlying mechanisms driving this invasion in vivo . Here, we develop a technique to noninvasively measure interstitial flow velocities in the glioma microenvironment of mice using dynamic contrast-enhanced magnetic resonance imaging (MRI), a common clinical technique...
September 2018: APL bioengineering
Boqi Dong, Liying Wang, Shu Nie, Xin Li, Yue Xiao, Lei Yang, Xiuping Meng, Peiyan Zhao, Cuiyun Cui, Liqun Tu, Wenting Lu, Wei Sun, Yongli Yu
The adjuvant effects of flagellin on regulation of immune response have been proved; whether flagellin could assist tumor cell lysate (TCL) to enhance anti-glioma immunity remains to be investigated. This study tests a hypothesis that therapeuticly intracranial administration with flagellin plus TCL enhances the effects of specific immunotherapy on glioma in mice. In this study, GL261 cells were transferred into C57BL/6 mice and the GL261-bearing mice were subcutaneously or intracranially inoculated with flagellin plus TCL, flagellin, TCL or saline...
November 15, 2018: Vaccine
Li Ma, Kangyu Lin, Guoqiang Chang, Yiwen Chen, Chen Yue, Qing Guo, Sicong Zhang, Zhiliang Jia, Tony T Huang, Aidong Zhou, Suyun Huang
Aberrant activation of β-catenin signaling is a critical driver for tumorigenesis, but the mechanism underlying this activation is not completely understood. In this study, we demonstrate a critical role of β-catenin signaling in stabilization of Enhancer of Zeste Homolog 2 (EZH2) and control of EZH2-mediated gene repression in oncogenesis. β-catenin/TCF4 activated transcription of the deubiquitinase USP1, which then interacted with and deubiquitinated EZH2 directly. USP1-mediated stabilization of EZH2 promoted its recruitment to the promoters of CDKN1B, RUNX3, and HOXA5, resulting in enhanced enrichment of histone H3K27me3 and repression of target gene expression...
November 13, 2018: Cancer Research
A V Dadeko, L Lilge, P Kaspler, T D Murav'eva, A M Starodubtcev, V M Kiselev, V V Zarubaev, G V Ponomarev
Photophysical and in vitro photocytotoxicity studies were performed for the photosensitizer Dimegine, a disodium salt 2.4-di(alpha-methoxyethyl)-deuteroporphyrin-IX with very low systemic toxicity. The singlet oxygen and luminescence quantum yield were ΦΔ  = 0,65 ± 0,06, and Φƒ =0,11 ± 0,01 respectively, and were independent of the excitation wavelength. The photobleaching coefficients for Dimegine dissolved in phosphate buffer (pH 7.4), and DMEM medium at concentration 2 μM/l and in phosphate buffer (pH 7...
November 6, 2018: Photodiagnosis and Photodynamic Therapy
Massimo Romani, Maria Pia Pistillo, Roberta Carosio, Anna Morabito, Barbara Banelli
Targeting the Immune Checkpoint molecules (ICs; CTLA-4, PD-1, PD-L1/2, and others) which provide inhibitory signals to T cells, dramatically improves survival in hard-to-treat tumors. The establishment of an immunosuppressive environment prevents endogenous immune response in glioblastoma; therefore, manipulating the host immune system seems a reasonable strategy also for this tumor. In glioma patients the accumulation of CD4+ /CD8+ T cells and Treg expressing high levels of CTLA-4 and PD-1, or the high expression of PD-L1 in glioma cells correlates with WHO high grade and short survival...
2018: Frontiers in Oncology
Michael Iv, Peyman Samghabadi, Samantha Holdsworth, Andrew Gentles, Paymon Rezaii, Griffith Harsh, Gordon Li, Reena Thomas, Michael Moseley, Heike E Daldrup-Link, Hannes Vogel, Max Wintermark, Samuel Cheshier, Kristen W Yeom
Purpose To investigate ferumoxytol-enhanced MRI as a noninvasive imaging biomarker of macrophages in adults with high-grade gliomas. Materials and Methods In this prospective study, adults with high-grade gliomas were enrolled between July 2015 and July 2017. Each participant was administered intravenous ferumoxytol (5 mg/kg) and underwent 3.0-T MRI 24 hours later. Two sites in each tumor were selected for intraoperative sampling on the basis of the degree of ferumoxytol-induced signal change. Susceptibility and the relaxation rates R2* (1/T2*) and R2 (1/T2) were obtained by region-of-interest analysis by using the respective postprocessed maps...
November 6, 2018: Radiology
Marissa Spino, Sylvia C Kurz, Luis Chiriboga, Jonathan Serrano, Briana Zeck, Namita Sen, Seema Patel, Guomiao Shen, Varshini Vasudevaraja, Aristotelis Tsirigos, Carter M Suryadevara, Joshua D Frenster, Kensuke Tateishi, Hiroaki Wakimoto, Rajan Jain, Howard A Riina, Theodore Nicolaides, Erik P Sulman, Daniel P Cahill, John G Golfinos, Kumiko Isse, Laura R Saunders, David Zagzag, Dimitris G Placantonakis, Matija Snuderl, Andrew S Chi
PURPOSE: Isocitrate dehydrogenase (IDH) mutant gliomas are a distinct glioma molecular subtype for which no effective molecularly-directed therapy exists. Low-grade gliomas, which are 80-90% IDH mutant, have high RNA levels of the cell surface Notch ligand DLL3. We sought to determine DLL3 expression by immunohistochemistry in glioma molecular subtypes and the potential efficacy of an anti-DLL3 antibody drug conjugate (ADC), rovalpituzumab tesirine (Rova-T), in IDH mutant glioma. EXPERIMENTAL DESIGN: We evaluated DLL3 expression by RNA using TCGA data and by immunohistochemistry in a discovery set of 63 gliomas and 20 non-tumor brain tissues and a validation set of 62 known IDH wildtype and mutant gliomas using a monoclonal anti-DLL3 antibody...
November 5, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Yuki Okuhashi, Mai Itoh, Shuji Tohda
BACKGROUND: Hedgehog (HH), WNT, NOTCH, and mechanistic target of rapamycin (mTOR) signalling pathways are known to regulate the progression of cancer; however, their interaction in leukaemia cells is not fully clarified. MATERIALS AND METHODS: Myeloid and T-lymphoblastic leukaemia cell lines (NB4, THP-1, Jurkat, and DND-41) were transfected with small interfering RNAs targeting the glioma-associated oncogene homolog 1 (GLI1) and catenin beta-1 (CTNNB1) genes involved in the regulation of HH and WNT pathways, respectively, and we examined cell proliferation and gene expression...
November 2018: Anticancer Research
Mallika P Weant, Caroline Mejías-De Jesús, Prakirthi Yerram
OBJECTIVES: To describe the immunotherapy approaches currently under investigation for the treatment of gliomas. To discuss the management of immune-related adverse effects. DATA SOURCES: Published literature, clinical trials, and oncology association guidance documents. CONCLUSION: There are numerous modalities of immune treatment currently being evaluated in patients with glioma, including peptide vaccines, dendritic cell vaccines, oncolytic viruses, CAR-T cells, and checkpoint inhibitor therapy...
November 2, 2018: Seminars in Oncology Nursing
David Castel, Cathy Philippe, Thomas Kergrohen, Martin Sill, Jane Merlevede, Emilie Barret, Stéphanie Puget, Christian Sainte-Rose, Christof M Kramm, Chris Jones, Pascale Varlet, Stefan M Pfister, Jacques Grill, David T W Jones, Marie-Anne Debily
Diffuse midline glioma (DMG), H3 K27M-mutant, is a new entity in the updated WHO classification grouping together diffuse intrinsic pontine gliomas and infiltrating glial neoplasms of the midline harboring the same canonical mutation at the Lysine 27 of the histones H3 tail.Two hundred and fifteen patients younger than 18 years old with centrally-reviewed pediatric high-grade gliomas (pHGG) were included in this study. Comprehensive transcriptomic (n = 140) and methylation (n = 80) profiling was performed depending on the material available, in order to assess the biological uniqueness of this new entity compared to other midline and hemispheric pHGG...
November 5, 2018: Acta Neuropathologica Communications
Anna C Filley, Mario Henriquez, Mahua Dey
T cell chimeric antigen receptor (CAR) technology has allowed for the introduction of a high degree of tumor selectivity into adoptive cell transfer therapies. Evolution of this technology has produced a robust antitumor immunotherapeutic strategy that has resulted in dramatic outcomes in liquid cancers. CAR-expressing T-cells (CARTs) targeting CD19 and CD20 have been successfully used in the treatment of hematologic malignancies, producing sustained tumor regressions in a majority of treated patients. These encouraging results have led to a historic and unprecedented FDA approval of CTL019, Novartis' CAR T-cell therapy for the treatment of children and young adults with relapsed or refractory B-cell acute lymphoblastic leukemia (ALL)...
2018: Frontiers in Oncology
Spencer C Behr, Javier E Villanueva-Meyer, Yan Li, Yung-Hua Wang, Junnian Wei, Anna Moroz, Julia Kl Lee, Jeffrey C Hsiao, Kenneth T Gao, Wendy Ma, Soonmee Cha, David M Wilson, Youngho Seo, Sarah J Nelson, Susan M Chang, Michael J Evans
Noninvasive tools that target tumor cells could improve the management of glioma. Cancer generally has a high demand for Fe(III), an essential nutrient for a variety of biochemical processes. We tested whether 68Ga-citrate, an Fe(III) biomimetic that binds to apo-transferrin in blood, detects glioma in preclinical models and patients using hybrid PET/MRI. Mouse PET/CT studies showed that 68Ga-citrate accumulates in subcutaneous U87MG xenografts in a transferrin receptor-dependent fashion within 4 hours after injection...
November 2, 2018: JCI Insight
Boris I Chobrutskiy, Saif Zaman, Wei Lue Tong, Andrea Diviney, George Blanck
The immune system plays an important role in cancer survival and disease progression, but the role of the immune system in lower grade glioma (LGG) is largely unknown METHODS: To investigate the relationship between lymphocyte infiltration into the LGG microenvironment and LGG survival, we used a genomics approach to recover productive V(D)J recombination sequences from primary tumor, whole exome sequence files available via the cancer genome atlas RESULTS: Increased T-cell receptor V(D)J read recovery, indicating increased T-lymphocyte infiltration into the primary tumor site, strongly correlated with decreased overall and disease-free survival; and with a more advanced cancer grade...
October 31, 2018: Journal of Neuro-oncology
Y Liu, F Li, Y T Yang, X D Xu, J S Chen, T L Chen, H J Chen, Y B Zhu, J Y Lin, Y Li, X M Xie, X L Sun, Y Q Ke
Vasculogenic mimicry (VM) refers to the fluid-conducting channels formed by aggressive tumor cells rather than endothelial cells (EC) with elevated expression of genes associated with vascularization. VM has been considered as one of the reasons that glioblastoma becomes resistant to anti-VEGF therapy. However, the molecular basis underlying VM formation remains unclear. Here we report that the insulin-like growth factor-binding protein 2 (IGFBP2) acts as a potent factor to enhance VM formation in glioma. Evidence showed that elevated IGFBP2 expression was positively related with VM formation in patients with glioma...
October 27, 2018: Oncogene
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