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https://read.qxmd.com/read/30759236/targeting-idh1-mutated-malignancies-with-nrf2-blockade
#1
Yang Liu, Yanxin Lu, Orieta Celiku, Aiguo Li, Qixin Wu, Yiqiang Zhou, Chunzhang Yang
Background: Neomorphic IDH1 mutations disrupt the redox balance by promoting reactive oxygen species (ROS) production. However, the mechanism by which IDH1-mutant cells maintain ROS homeostasis remains elusive. It is also not known whether reprogrammed ROS homeostasis establishes targetable vulnerability in IDH1-mutated cancers. Methods: We investigated ROS homeostasis in wild-type (GSC827, GSC923, GSC627, and GSC711) and IDH1-mutated cells (IDH1R132C- and IDH1R132H-transduced U87, U251; MGG152, and TS603 cells)...
February 12, 2019: Journal of the National Cancer Institute
https://read.qxmd.com/read/30755443/t-type-cav3-1-channels-mediate-progression-and-chemotherapeutic-resistance-in-glioblastoma
#2
Anna Visa, Marta C Sallán, Oscar Maiques, Lía Alza, Elisabet Talavera, Ricard López-Ortega, Maria Santacana, Judit Herreros, Carles Cantí
T-type Ca2+ channels (TTCC) have been identified as key regulators of cancer cell cycle and survival. In vivo studies in glioblastoma (GBM) murine xenografts have shown that drugs able to block TTCC in vitro (such as tetralol derivatives mibefradil/NNC-55-096, or different 3,4-dihydroquinazolines) slow tumor progression. However, currently available TTCC pharmacological blockers have limited selectivity for TTCC, and are unable to distinguish between TTCC isoforms. Here we analyzed the expression of TTCC transcripts in human GBM cells and show a prevalence of Cav3...
February 12, 2019: Cancer Research
https://read.qxmd.com/read/30745846/a-novel-role-of-cx43-composed-gjic-in-pdt-phototoxicity-an-implication-of-cx43-for-the-enhancement-of-pdt-efficacy
#3
Deng-Pan Wu, Li-Ru Bai, Yan-Fang Lv, Yan Zhou, Chun-Hui Ding, Si-Man Yang, Fan Zhang, Jin-Lan Huang
In spite of initially promising responses, 5-year recurrence after photodynamic therapy (PDT) sustains high level and an increase in PDT effectiveness is needed. It has been demonstrated that gap junctional intercellular communication (GJIC) formed by Connexin (Cx)43 could improve the transfer of "death signal" between cells, thereby causing the enhancement of cytotoxicity of chemotherapeutics and suicide gene therapy. Nevertheless, whether Cx43-composed GJIC has an effect on PDT phototoxicity remains unknown...
2019: International Journal of Biological Sciences
https://read.qxmd.com/read/30740906/activation-of-ptgs2-nf-%C3%AE%C2%BAb-signaling-pathway-enhances-radiation-resistance-of-glioma
#4
Cheng Tan, Liang Liu, Xiaoyang Liu, Ling Qi, Weiyao Wang, Guifang Zhao, Libo Wang, Yimeng Dai
OBJECTIVE: We focused on the effects of PTGS2/NF-κB signaling pathway on the radiation resistance of glioma in the study. METHODS: We downloaded the microarray data from the Gene Expression Omnibus (GEO) database. We verified transfection successfully through QRT-PCR analysis. Immunofluorescence was used to detect γH2AX content under 2 Gy radiation. The survival rates of cells under 2 Gy irradiation were tested by clonogenic survival assay. Flow cytometry was used to detect cell cycle...
February 10, 2019: Cancer Medicine
https://read.qxmd.com/read/30736838/fus-circ_002136-mir-138-5p-sox13-feedback-loop-regulates-angiogenesis-in-glioma
#5
Zhenwei He, Xuelei Ruan, Xiaobai Liu, Jian Zheng, Yunhui Liu, Libo Liu, Jun Ma, Lianqi Shao, Di Wang, Shuyuan Shen, Chunqing Yang, Yixue Xue
BACKGROUND: Angiogenesis plays a critical role in the progression of glioma. Previous studies have indicated that RNA-binding proteins (RBPs) interact with RNAs and participate in the regulation of the malignant behaviors of tumors. As a type of endogenous non-coding RNAs, circular RNAs (circRNAs) are abnormally expressed in various cancers and are involved in diverse tumorigeneses including angiogenesis. METHODS: The expression levels of FUS, circ_002136, miR-138-5p, SOX13, and SPON2 were determined using quantitative real-time PCR (qRT-PCR) and western blot...
February 8, 2019: Journal of Experimental & Clinical Cancer Research: CR
https://read.qxmd.com/read/30736462/circsmarca5-regulates-vegfa-mrna-splicing-and-angiogenesis-in-glioblastoma-multiforme-through-the-binding-of-srsf1
#6
Davide Barbagallo, Angela Caponnetto, Duilia Brex, Federica Mirabella, Cristina Barbagallo, Giovanni Lauretta, Antonio Morrone, Francesco Certo, Giuseppe Broggi, Rosario Caltabiano, Giuseppe M Barbagallo, Vittoria Spina-Purrello, Marco Ragusa, Cinzia Di Pietro, Thomas B Hansen, Michele Purrello
Circular RNAs are a large group of RNAs whose cellular functions are still being investigated. We recently proposed that circSMARCA5 acts as sponge for the splicing factor Serine and Arginine Rich Splicing Factor 1 (SRSF1) in glioblastoma multiforme (GBM). After demonstrating by RNA immunoprecipitation a physical interaction between SRFS1 and circSMARCA5, we assayed by real-time PCR in a cohort of 31 GBM biopsies and 20 unaffected brain parenchyma controls (UC) the expression of total, pro-angiogenic (Iso8a) and anti-angiogenic (Iso8b) mRNA isoforms of Vascular Endothelial Growth Factor A (VEGFA), a known splicing target of SRSF1...
February 7, 2019: Cancers
https://read.qxmd.com/read/30718560/laser-synthesized-tin-nanoparticles-as-promising-plasmonic-alternative-for-biomedical-applications
#7
Anton A Popov, Gleb Tselikov, Noé Dumas, Charlotte Berard, Khaled Metwally, Nicola Jones, Ahmed Al-Kattan, Benoit Larrat, Diane Braguer, Serge Mensah, Anabela Da Silva, Marie-Anne Estève, Andrei V Kabashin
Exhibiting a red-shifted absorption/scattering feature compared to conventional plasmonic metals, titanium nitride nanoparticles (TiN NPs) look as very promising candidates for biomedical applications, but these applications are still underexplored despite the presence of extensive data for conventional plasmonic counterparts. Here, we report the fabrication of ultrapure, size-tunable TiN NPs by methods of femtosecond laser ablation in liquids and their biological testing. We show that TiN NPs demonstrate strong and broad plasmonic peak around 640-700 nm with a significant tail over 800 nm even for small NPs sizes (<7 nm)...
February 4, 2019: Scientific Reports
https://read.qxmd.com/read/30717385/degradation-of-mitochondria-and-oxidative-stress-as-the-main-mechanism-of-toxicity-of-pristine-graphene-on-u87-glioblastoma-cells-and-tumors-and-hs-5-cells
#8
Sławomir Jaworski, Barbara Strojny, Ewa Sawosz, Mateusz Wierzbicki, Marta Grodzik, Marta Kutwin, Karolina Daniluk, André Chwalibog
Due to the development of nanotechnologies, graphene and graphene-based nanomaterials have attracted immense scientific interest owing to their extraordinary properties. Graphene can be used in many fields, including biomedicine. To date, little is known about the impact graphene may have on human health in the case of intentional exposure. The present study was carried out on U87 glioma cells and non-cancer HS-5 cell lines as in vitro model and U87 tumors cultured on chicken embryo chorioallantoic membrane as in vivo model, on which the effects of pristine graphene platelets (GPs) were evaluated...
February 2, 2019: International Journal of Molecular Sciences
https://read.qxmd.com/read/30714532/antioxidant-effects-of-oleuropein-on-hydrogen-peroxide-induced-neuronal-stress-an-in-vitro-study
#9
Altug Kucukgul, Mehmet Mustafa Isgor, Vesile Duzguner, Azime Kucukgul, Meryem Nur Atabay
BACKGROUND: Persistent oxidative stress can lead to chronic inflammation and mediate most chronic diseases including neurological disorders. Oleuropein has been shown to be a potent antioxidant molecule in olive oil leaf having antioxidative properties. OBJECTIVE: The aim of this study was to investigate the protective effects of oleuropein against oxidative stress in human glioblastoma cells. METHOD: Human glioblastoma cells (U87) were pretreated with oleuropein (OP) essential oil 10 µM...
February 1, 2019: Anti-inflammatory & Anti-allergy Agents in Medicinal Chemistry
https://read.qxmd.com/read/30712887/molecular-mechanism-of-ssfa2-deletion-inhibiting-cell-proliferation-and-promoting-cell-apoptosis-in-glioma
#10
Aihua Zhu, Xuetao Li, Haibin Wu, Zongning Miao, Fenglai Yuan, Feng Zhang, Bei Wang, Youxin Zhou
Gliomas are the most common primary brain malignant tumors in humans. Glioblastoma multiforme(GBM) is the most malignant intracranial tumor with a relatively poor prognosis. There promote us to find effective anti-cancer therapies to reduce cancer mortality. By using bioinformatic analysis, we found SSFA2 as a gene with elevated expression in the glioma tissues. We detected the expression of SSFA2 in glioma tissues and in the glioma cell lines, as well as in normal brain tissues. SSFA2 expression was higher in glioma tissues, especially in glioblastoma multiforme than normal brain tissues...
December 31, 2018: Pathology, Research and Practice
https://read.qxmd.com/read/30705757/ph-as-a-potential-therapeutic-target-to-improve-temozolomide-antitumor-efficacy-a-mechanistic-modeling-study
#11
Angélique Stéphanou, Annabelle Ballesta
Despite intensive treatments including temozolomide (TMZ) administration, glioblastoma patient prognosis remains dismal and innovative therapeutic strategies are urgently needed. A systems pharmacology approach was undertaken to investigate TMZ pharmacokinetics-pharmacodynamics (PK-PD) incorporating the effect of local pH, tumor spatial configuration and micro-environment. A hybrid mathematical framework was designed coupling ordinary differential equations describing the intracellular reactions, with a spatial cellular automaton to individualize the cells...
February 2019: Pharmacology Research & Perspectives
https://read.qxmd.com/read/30704035/challenges-and-contradictions-of-metal-nano-particle-applications-for-radio-sensitivity-enhancement-in-cancer-therapy
#12
Eva Pagáčová, Lenka Štefančíková, Franz Schmidt-Kaler, Georg Hildenbrand, Tomáš Vičar, Daniel Depeš, Jin-Ho Lee, Felix Bestvater, Sandrine Lacombe, Erika Porcel, Stéphane Roux, Frederik Wenz, Olga Kopečná, Iva Falková, Michael Hausmann, Martin Falk
From the very beginnings of radiotherapy, a crucial question persists with how to target the radiation effectiveness into the tumor while preserving surrounding tissues as undamaged as possible. One promising approach is to selectively pre-sensitize tumor cells by metallic nanoparticles. However, though the "physics" behind nanoparticle-mediated radio-interaction has been well elaborated, practical applications in medicine remain challenging and often disappointing because of limited knowledge on biological mechanisms leading to cell damage enhancement and eventually cell death...
January 30, 2019: International Journal of Molecular Sciences
https://read.qxmd.com/read/30703492/cytotoxicity-of-the-crude-extract-and-constituents-of-the-bark-of-fagara-tessmannii-towards-multi-factorial-drug-resistant-cancer-cells
#13
Armelle T Mbaveng, Francois Damen, İlhami Çelik, Pierre Tane, Victor Kuete, Thomas Efferth
ETHNOPHARMACOLOGICAL RELEVANCE: Fagara tessmannii Engl. is an African medicinal plant used in Cameroonian traditional medicine to treat various types of cancers. AIM OF THE STUDY: This work was designed to determine the cytotoxicity of the crude extract (FTB), fractions (FTBa-d) and compounds isolated from the bark of Fagara tessmannii, namely lupeol (1), fagaramide (2), zanthoxyline (3), hesperidin (4), nitidine chloride (5), fagaridine chloride (6), and β-sitosterol-3-O-β-D -glucopyranoside (7)...
January 28, 2019: Journal of Ethnopharmacology
https://read.qxmd.com/read/30700502/a-cyclic-peptide-reproducing-the-%C3%AE-1-helix-of-vegf-b-binds-to-vegfr-1-and-vegfr-2-and-inhibits-angiogenesis-and-tumor-growth
#14
Elham Assareh, Faramarz Mehrnejad, Kamran Mansouri, Ahmad Reza Esmaeili Rastaghi, Hossein Naderi-Manesh, S Mohsen Asghari
Vascular endothelial growth factors (VEGFs) and their receptors (VEGFRs) are pivotal regulators of angiogenesis. VEGF-VEGFR system is therefore an important target of anti-angiogenesis therapy. Based on the X-ray structure of VEGF-B/VEGFR-1 D2, we designed a cyclic peptide (known as VGB1) reproducing the α1 helix and its adjacent region to interfere with signaling through to VEGFR-1. Unexpectedly, VGB1 bound VEGFR-2 in addition to VEGFR-1, leading to inhibition of VEGF-stimulated proliferation of Human Umbilical Vein Endothelial Cells (HUVECs) and 4T1 murine mammary carcinoma cells, which express VGEFR-1 and VEGFR-2, and U87 glioblastoma cells that mostly express VEGFR-2...
January 30, 2019: Biochemical Journal
https://read.qxmd.com/read/30698450/targeted-and-synergic-glioblastoma-treatment-multifunctional-nanoparticles-delivering-verteporfin-as-adjuvant-therapy-for-temozolomide-chemotherapy
#15
Diogo S Pellosi, Leonardo B de Paula, Maryanne T de Melo, Antonio C Tedesco
Despite advances in cancer therapies, glioblastoma multiforme e treatment remains inefficient due to the brain-blood barrier (BBB) inhibitory activity and to the low Temozolomide (TMZ) chemotherapeutic selectivity. To improve therapeutic outcomes, in this work we propose two strategies: (i) photodynamic therapy (PDT) as adjuvant treatment and (ii) engineering of multifunctional theranostic/targeted nanoparticles (m-NPs) that integrate biotin as a targeting moiety with rhodamine-B as a theranostic agent in Pluronic P85/F127 copolymers...
January 30, 2019: Molecular Pharmaceutics
https://read.qxmd.com/read/30697890/single-molecule-force-measurement-guides-the-design-of-multivalent-ligand-with-picomolar-affinity
#16
Zhen Yang, Sheng Jiang, Feng Li, Yatao Qiu, Jianhua Gu, Roderic I Pettigrew, Mauro Ferrari, Dale J Hamilton, Zheng Li
Interaction of multiple entities and receptors, or multivalency is widely applied to achieve high affinity ligands for diagnostic and therapeutic purpose. However, lack of knowledge on receptor distribution in living subjects remains a challenge for rational structure design. Here, we developed a force measurement platform to probe the distribution and distance of the cell surface vascular endothelial growth factor receptors (VEGFR) in live cells, and used this to assess the geometry of appropriate linkers for distinct multivalent binding modes...
January 29, 2019: Angewandte Chemie
https://read.qxmd.com/read/30694423/a-novel-3d-in-vitro-model-of-glioblastoma-reveals-resistance-to-temozolomide-which-was-potentiated-by-hypoxia
#17
Ahmed Musah-Eroje, Sue Watson
PURPOSE: Glioblastoma (GBM) is the most common invasive malignant brain tumour in adults. It is traditionally investigated in vitro by culturing cells as a monolayer (2D culture) or as neurospheres (clusters enriched in cancer stem cells) but neither system accurately reflects the complexity of the three-dimensional (3D) chemoresistant microenvironment of GBM. MATERIALS AND METHODS: Using three GBM cell-lines (U87, U251, and SNB19), the effect of culturing cells in a Cultrex-based basement membrane extract (BME) [3D Tumour Growth Assay (TGA)] on morphology, gene expression, metabolism, and temozolomide chemoresistance was investigated...
January 29, 2019: Journal of Neuro-oncology
https://read.qxmd.com/read/30680690/fabp7-protects-astrocytes-against-ros-toxicity-via-lipid-droplet-formation
#18
Ariful Islam, Yoshiteru Kagawa, Hirofumi Miyazaki, Subrata Kumar Shil, Banlanjo A Umaru, Yuki Yasumoto, Yui Yamamoto, Yuji Owada
Fatty acid-binding proteins (FABPs) bind and internalize long-chain fatty acids, controlling lipid dynamics. Recent studies have proposed the involvement of FABPs, particularly FABP7, in lipid droplet (LD) formation in glioma, but the physiological significance of LDs is poorly understood. In this study, we sought to examine the role of FABP7 in primary mouse astrocytes, focusing on its protective effect against reactive oxygen species (ROS) stress. In FABP7 knockout (KO) astrocytes, ROS induction significantly decreased LD accumulation, elevated ROS toxicity, and impaired thioredoxin (TRX) but not peroxiredoxin 1 (PRX1) signalling compared to ROS induction in wild-type astrocytes...
January 24, 2019: Molecular Neurobiology
https://read.qxmd.com/read/30669581/pka-at-a-cross-road-of-signaling-pathways-involved-in-the-regulation-of-glioblastoma-migration-and-invasion-by-the-neuropeptides-vip-and-pacap
#19
Souheyla Bensalma, Soumaya Turpault, Annie-Claire Balandre, Madryssa De Boisvilliers, Afsaneh Gaillard, Corinne Chadéneau, Jean-Marc Muller
Glioblastoma (GBM) remains an incurable disease, mainly due to the high migration and invasion potency of GBM cells inside the brain. PI3K/Akt, Sonic Hedgehog (SHH), and PKA pathways play major regulatory roles in the progression of GBM. The vasoactive intestinal peptide (VIP) family of neuropeptides and their receptors, referred in this article as the "VIP-receptor system", has been reported to regulate proliferation, differentiation, and migration in a number of tumor cell types and more particularly in GBM cells...
January 21, 2019: Cancers
https://read.qxmd.com/read/30659115/tau-regulates-the-microtubule-dependent-migration-of-glioblastoma-cells-via-the-rho-rock-signaling-pathway
#20
Gilles Breuzard, Alessandra Pagano, Sonia Bastonero, Soazig Malesinski, Fabrice Parat, Pascale Barbier, Vincent Peyrot, Hervé Kovacic
The pathological significance of Tau in mechanisms driving cell migration in glioblastoma is unclear. Using shRNA approach to deplete microtubule-stabilizing Tau in U87 cells, we determined its impact on cytoskeletal coordination during migration. We demonstrated here that the motility of Tau-down-expressing cells (shTau) was significantly 36% lower than control cells. The shTau cells displayed weakly changed motility in the presence of nocodazole inhibiting microtubule formation. Such reduced motility of shTau cells was characterized by a 28% lower amount of microtubules bundles upon non-adhesive edges of the tails...
January 18, 2019: Journal of Cell Science
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