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https://www.readbyqxmd.com/read/29687002/identification-of-key-candidate-proteins-and-pathways-associated-with-temozolomide-resistance-in-glioblastoma-based-on-subcellular-proteomics-and-bioinformatical-analysis
#1
Guo-Zhong Yi, Wei Xiang, Wen-Yan Feng, Zi-Yang Chen, Yao-Min Li, Sheng-Ze Deng, Man-Lan Guo, Liang Zhao, Xue-Gang Sun, Min-Yi He, Song-Tao Qi, Ya-Wei Liu
TMZ resistance remains one of the main reasons why treatment of glioblastoma (GBM) fails. In order to investigate the underlying proteins and pathways associated with TMZ resistance, we conducted a cytoplasmic proteome research of U87 cells treated with TMZ for 1 week, followed by differentially expressed proteins (DEPs) screening, KEGG pathway analysis, protein-protein interaction (PPI) network construction, and validation of key candidate proteins in TCGA dataset. A total of 161 DEPs including 65 upregulated proteins and 96 downregulated proteins were identified...
2018: BioMed Research International
https://www.readbyqxmd.com/read/29683790/multicenter-phase-ib-trial-of-carboxyamidotriazole-orotate-and-temozolomide-for-recurrent-and-newly-diagnosed-glioblastoma-and-other-anaplastic-gliomas
#2
Antonio Omuro, Kathryn Beal, Katharine McNeill, Robert J Young, Alissa Thomas, Xuling Lin, Robert Terziev, Thomas J Kaley, Lisa M DeAngelis, Mariza Daras, Igor T Gavrilovic, Ingo Mellinghoff, Eli L Diamond, Andrew McKeown, Malbora Manne, Andrew Caterfino, Krishna Patel, Linda Bavisotto, Greg Gorman, Michael Lamson, Philip Gutin, Viviane Tabar, Debyani Chakravarty, Timothy A Chan, Cameron W Brennan, Elizabeth Garrett-Mayer, Rashida A Karmali, Elena Pentsova
Purpose Carboxyamidotriazole orotate (CTO) is a novel oral inhibitor of non-voltage-dependent calcium channels with modulatory effects in multiple cell-signaling pathways and synergistic effects with temozolomide (TMZ) in glioblastoma (GBM) models. We conducted a phase IB study combining CTO with two standard TMZ schedules in GBM. Methods In cohort 1, patients with recurrent anaplastic gliomas or GBM received escalating doses of CTO (219 to 812.5 mg/m2 once daily or 600 mg fixed once-daily dose) combined with TMZ (150 mg/m2 5 days during each 28-day cycle)...
April 23, 2018: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/29671197/distinct-response-to-gdf15-knockdown-in-pediatric-and-adult-glioblastoma-cell-lines
#3
Mirella Baroni, Suely Kazue Nagahashi Marie, Paola Fernanda Fedatto, Augusto Faria Andrade, Veridiana Kill Suazo, Gustavo Alencastro Veiga Cruzeiro, Rosane de Paula Queiroz, Luiz Gonzaga Tone, Carlos Alberto Scrideli
INTRODUCTION: Glioblastoma (GBM) is the most common malignant primary brain tumor affecting adults. In pediatric patients, GBM exhibits genetic variations distinct from those identified in the adult GBM phenotype. This tumor exhibits complex genetic changes leading to malignant progression and resistance to standard therapies including radiotherapy and temozolomide treatment. The GDF15 gene codes for a growth factor whose expression is altered in the presence of inflammations and malignancies...
April 18, 2018: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/29660909/the-effect-of-trimetazidine-in-reducing-the-ischemia-reperfusion-injury-in-rat-epigastric-skin-flaps
#4
Laura Petrovics, Tibor Nagy, Peter Hardi, Laura Bognar, Gabor Pavlovics, Gyorgy Tizedes, Ildiko Takacs, Gabor Jancso
BACKGROUND: Ischemia-reperfusion injury may lead to insufficient microcirculation and results in partial flap loss during the free flap surgeries. OBJECTIVE: This study aimed to investigate the effect of trimetazidine (TMZ) on oxidative stress, inflammation and histopathological changes, using the epigastric skin flap model in rats. METHODS: 40 male Wistar rats were used, that were divided into four groups. Control group, non-treated ischemic (I/R)-group and two trimetazidine treated groups (preischemically, postischemically) were established...
April 13, 2018: Clinical Hemorheology and Microcirculation
https://www.readbyqxmd.com/read/29658588/autophagy-inhibition-potentiates-saha%C3%A2-mediated-apoptosis-in-glioblastoma-cells-by-accumulation-of-damaged-mitochondria
#5
Kovooru Lohitesh, Heena Saini, Abhilasha Srivastava, Sudeshna Mukherjee, Aniruddha Roy, Rajdeep Chowdhury
Glioblastoma multiforme (GBM), often referred to as a grade IV astrocytoma, is the most invasive type of tumor arising from glial cells. The main treatment options for GBM include surgery, radiation and chemotherapy. However, these treatments tend to be only palliative rather than curative. Poor prognosis of GBM is due to its marked resistance to standard therapy. Currently, temozolomide (TMZ), an alkylating agent is used for treatment of GBM. However, GBM cells can repair TMZ‑induced DNA damage and therefore diminish the therapeutic efficacy of TMZ...
April 16, 2018: Oncology Reports
https://www.readbyqxmd.com/read/29658349/biodegradable-hybrid-structured-nanofibrous-membrane-supported-chemoprotective-gene-therapy-enhances-chemotherapy-tolerance-and-efficacy-in-malignant-glioma-rats
#6
Shih-Jung Liu, Tao-Chieh Yang, Shun-Tai Yang, Ying-Chun Chen, Yuan-Yun Tseng
Chemotherapy is ineffective for treating malignant glioma (MG) because of the low therapeutic levels of pharmaceuticals in tumour tissues and the well-known tumour resistance. The resistance to alkylators is modulated by the DNA repair protein O6 -alkylguanine-DNA alkyltransferase (AGT). O6 -benzylguanine (O6 -BG) can irreversibly inactivate AGT by competing with O6 -methylguanine and has been confirmed to increase the therapeutic activity of alkylators. We developed hybrid-structured poly[(d,l)-lactide-co-glycolide] nanofibrous membranes (HSNMs) that enable the sequential and sustained release of O6 -BG and two alkylators (carmustine and temozolomide [TMZ])...
April 16, 2018: Artificial Cells, Nanomedicine, and Biotechnology
https://www.readbyqxmd.com/read/29650288/duocarmycin-sa-a-potent-antitumor-antibiotic-sensitizes-glioblastoma-cells-to-proton-radiation
#7
Kristopher E Boyle, Dale L Boger, Andrew Wroe, Marcelo Vazquez
New treatment modalities for glioblastoma multiforme (GBM) are urgently needed. Proton therapy is considered one of the most effective forms of radiation therapy for GBM. DNA alkylating agents such as temozolomide (TMZ) are known to increase the radiosensitivity of GBM to photon radiation. TMZ is a fairly impotent agent, while duocarmycin SA (DSA) is an extremely potent cytotoxic agent capable of inducing a sequence-selective alkylation of duplex DNA. Here, the effects of sub-nM concentrations of DSA on the radiosensitivity of a human GBM cell line (U-138) to proton irradiation were examined...
April 4, 2018: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29648580/bevacizumab-plus-hypofractionated-radiotherapy-versus-radiotherapy-alone-in-elderly-patients-with-glioblastoma-the-randomized-open-label-phase-ii-arte-trial
#8
H-G Wirsching, G Tabatabai, U Roelcke, A F Hottinger, F Jörger, A Schmid, L Plasswilm, D Schrimpf, C Mancao, D Capper, K Conen, T Hundsberger, F Caparrotti, R von Moos, C Riklin, J Felsberg, P Roth, D T W Jones, S Pfister, E J Rushing, L Abrey, G Reifenberger, L Held, A von Deimling, A Ochsenbein, M Weller
Background: The addition of bevacizumab to temozolomide-based chemoradiotherapy (TMZ/RT→TMZ) did not prolong overall survival (OS) in patients with newly diagnosed glioblastoma in phase III trials. Elderly and frail patients are underrepresented in clinical trials, but early reports suggested preferential benefit in this population. Patients and Methods: ARTE was a 2:1 randomized, multi-center, open-label, non-comparative phase II trial of hypofractionated RT (40 Gy in 15 fractions) with bevacizumab (10 mg/kg x 14 days) (arm A, N = 50) or without bevacizumab (arm B, N = 25) in patients with newly diagnosed glioblastoma aged ≥65 years...
April 10, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29648554/discovery-of-quinazoline-2-4-1h-3h-dione-derivatives-as-novel-parp-1-2-inhibitors-design-synthesis-and-their-antitumor-activity
#9
Jie Zhou, Ming Ji, Haiping Yao, Ran Cao, Hailong Zhao, Xiaoyu Wang, Xiaoguang Chen, Bailing Xu
Novel quinazoline-2,4(1H,3H)-dione derivatives bearing a 3-amino pyrrolidine moiety were designed and synthesized as PARP-1/2 inhibitors. Structure-activity relationships were examined which revealed a number of potent PARP-1/2 inhibitors with moderate selectivity toward PARP-1 over PARP-2. These compounds had IC50 values against PARP-1 at the 10-9 M level and against PARP-2 at the 10-8 M level. Among all the synthesized compounds, compounds 10 and 11 displayed strong cytotoxicities which are either used as a single agent or in combination with temozolomide (TMZ) in MX-1 cells (10, IC50 < 3...
April 12, 2018: Organic & Biomolecular Chemistry
https://www.readbyqxmd.com/read/29644711/outlining-involvement-of-stem-cell-program-in-regulation-of-o6-methylguanine-dna-methyltransferase-and-development-of-temozolomide-resistance-in-glioblastoma-an-editorial-highlight-for-transcriptional-control-of-o-6-methylguanine-dna-methyltransferase-expression
#10
EDITORIAL
Anastasia Chumakova, Justin D Lathia
Glioblastoma is a malignant brain tumor that inevitably develops resistance to standard of care drug temozolomide (TMZ) due to a population of cells called cancer stem cells (CSCs). These cells utilize progenitor cell signaling programs and develop robust DNA repair machinery. In this editorial highlight we focus on stem cell regulation of TMZ resistance and discuss findings of Happold et al. () that outline direct transcriptional regulation of DNA repair enzyme O6-methylguanine DNA methyltransferase (MGMT) in glioblastoma CSCs through NFkB activation...
March 2018: Journal of Neurochemistry
https://www.readbyqxmd.com/read/29628799/clinical-and-immunological-correlates-of-long-term-survival-in-glioblastoma
#11
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/29619003/the-clinical-significance-of-o-6-methylguanine-dna-methyltransferase-promoter-methylation-status-in-adult-patients-with-glioblastoma-a-meta-analysis
#12
Yu-Hang Zhao, Ze-Fen Wang, Chang-Jun Cao, Hong Weng, Cheng-Shi Xu, Kai Li, Jie-Li Li, Jing Lan, Xian-Tao Zeng, Zhi-Qiang Li
Background and objective: Promoter status of O6 -methylguanine-DNA methyltransferase ( MGMT ) has been widely established as a clinically relevant factor in glioblastoma (GBM) patients. However, in addition to varied therapy schedule, the prognosis of GBM patients is also affected by variations of age, race, primary or recurrent tumor. This study comprehensively investigated the association between MGMT promoter status and prognosis in overall GBM patients and in different GBM subtype including new diagnosed patients, recurrent patients and elderly patients...
2018: Frontiers in Neurology
https://www.readbyqxmd.com/read/29616127/therapeutic-approach-in-glioblastoma-multiforme-with-primitive-neuroectodermal-tumor-components-case-report-and-review-of-the-literature
#13
Arsela Prelaj, Sara Elena Rebuzzi, Giovanni Caffarena, Julio Rodrigo Giròn Berrìos, Silvia Pecorari, Carmela Fusto, Alessandro Caporlingua, Federico Caporlingua, Annamaria Di Palma, Fabio Massimo Magliocca, Maurizio Salvati, Silverio Tomao, Vincenzo Bianco
Glioblastoma multiforme (GBM) is the most common and aggressive malignant glioma that is treated with first-line therapy, using surgical resection followed by local radiotherapy and concomitant/adjuvant temozolomide (TMZ) treatment. GBM is characterised by a high local recurrence rate and a low response to therapy. Primitive neuroectodermal tumour (PNET) of the brain revealed a low local recurrence rate; however, it also exhibited a high risk of cerebrospinal fluid (CSF) dissemination. PNET is treated with surgery followed by craniospinal irradiation (CSI) and platinum-based chemotherapy in order to prevent CSF dissemination...
May 2018: Oncology Letters
https://www.readbyqxmd.com/read/29614990/improved-effects-of-honokiol-on-temozolomide-induced-autophagy-and-apoptosis-of-drug-sensitive-and-tolerant-glioma-cells
#14
Chung-Ching Chio, Kung-Yen Chen, Cheng-Kuei Chang, Jian-Ying Chuang, Chih-Chung Liu, Shing-Hwa Liu, Ruei-Ming Chen
BACKGROUND: Temozolomide (TMZ)-induced side effects and drug tolerance to human gliomas are still challenging issues now. Our previous studies showed that honokiol, a major bioactive constituent of Magnolia officinalis (Houpo), is safe for normal brain cells and can kill human glioma cells. This study was further aimed to evaluate the improved effects of honokiol and TMZ on drug-sensitive and -resistant glioma cells and the possible mechanisms. METHODS: TMZ-sensitive human U87-MG and murine GL261 glioma cells and TMZ-resistant human U87-MR-R9 glioma cells were exposed to honokiol and TMZ, and cell viability and LC50 of honokiol were assayed...
April 3, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29606504/a-chimeric-antibody-against-ackr3-cxcr7-in-combination-with-tmz-activates-immune-responses-and-extends-survival-in-mouse-gbm-models
#15
Nicole Salazar, Jeffrey C Carlson, Kexin Huang, Yayue Zheng, Cecilia Oderup, Julia Gross, Andrew D Jang, Thomas M Burke, Susanna Lewén, Alexander Scholz, Serina Huang, Leona Nease, Jon Kosek, Michel Mittelbronn, Eugene C Butcher, Hua Tu, Brian A Zabel
Glioblastoma (GBM) is the least treatable type of brain tumor, afflicting over 15,000 people per year in the United States. Patients have a median survival of 16 months, and over 95% die within 5 years. The chemokine receptor ACKR3 is selectively expressed on both GBM cells and tumor-associated blood vessels. High tumor expression of ACKR3 correlates with poor prognosis and potential treatment resistance, making it an attractive therapeutic target. We engineered a single chain FV-human FC-immunoglobulin G1 (IgG1 ) antibody, X7Ab, to target ACKR3 in human and mouse GBM cells...
March 6, 2018: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/29600221/prognostic-factors-and-outcomes-in-anaplastic-gliomas-an-institutional-experience
#16
Deepthi Valiyaveettil, Monica Malik, Deepa Joseph, Syed Fayaz Ahmed, Syed Akram Kothwal
Background: There is lack of clear evidence and treatment guidelines for anaplastic gliomas (AGs) with very few studies focusing exclusively on these patients. The aim of the study was to analyze the clinical profile and survival in these patients. Materials and Methods: Patients of AGs treated with radiation and concurrent ± adjuvant chemotherapy from January 2010 to December 2015 were analyzed. Statistical analysis was done using SPSS version 20 software. Results: A total of 100 patients were included in the study...
January 2018: South Asian Journal of Cancer
https://www.readbyqxmd.com/read/29599977/computer-aided-design-of-temozolomide-derivatives-based-on-alkylglycerone-phosphate-synthase-structure-with-isothiocyanate-and-their-pharmacokinetic-toxicity-prediction-and-anti-tumor-activity-in-vitro
#17
Bing Yang, Xiaobo Li, Lu He, Yu Zhu
Despite the development of temozolomide (TMZ), a novel type of glioma therapeutic drug, malignant glioma remains to cause severe damage to human health. The present study aimed to utilize the molecular biological differences between tumor and normal cells to design TMZ derivatives with improved selectivity and targeting using computer-aided drug design (CADD). Taking alkylglycerone phosphate synthase (AGPS) as a target, a 3D structure-activity relationship model was built using CADD technology; molecular docking of isothiocyanate (ITC) and TMZ compounds was conducted; ITC-TMZ derivatives were designed; and predictions on the absorption, distribution, metabolism and excretion (ADME) processes and toxicity of the ITC-TMZ derivatives were established in order to obtain improved understanding of the structure-activity relationship of the candidate compounds...
March 2018: Biomedical Reports
https://www.readbyqxmd.com/read/29582250/opposite-interplay-between-the-canonical-wnt-%C3%AE-catenin-pathway-and-ppar-gamma-a-potential-therapeutic-target-in-gliomas
#18
REVIEW
Alexandre Vallée, Yves Lecarpentier, Rémy Guillevin, Jean-Noël Vallée
In gliomas, the canonical Wingless/Int (WNT)/β-catenin pathway is increased while peroxisome proliferator-activated receptor gamma (PPAR-γ) is downregulated. The two systems act in an opposite manner. This review focuses on the interplay between WNT/β-catenin signaling and PPAR-γ and their metabolic implications as potential therapeutic target in gliomas. Activation of the WNT/β-catenin pathway stimulates the transcription of genes involved in proliferation, invasion, nucleotide synthesis, tumor growth, and angiogenesis...
March 26, 2018: Neuroscience Bulletin
https://www.readbyqxmd.com/read/29575236/dmc-is-not-better-than-tmz-on-intracranial-anti-glioma-effects
#19
Lei Shi, Guan Sun
Previous studies showed Demethoxycurcumin (DMC) has stronger anti-glioma and anti-GSCs effects both in vitro and in vivo. In addition, DMC seems to be lower toxicity than TMZ on nude mice. However, this conclusion was confirmed to be wrong in this study. We have evaluated the antitumor efficacy of DMC or TMZ treatment by an orthotopic glioblastoma xenograft model. Nude mice were injected with U87MG-luc cells in the caudate nucleus of the brain and treated with DMC (30 mg/kg q.d.) or TMZ (10 mg/kg q.d.) by intraperitoneal injection...
March 25, 2018: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29574277/xrcc3-contributes-to-temozolomide-resistance-of-glioblastoma-cells-by-promoting-dna-double-strand-break-repair
#20
Wynand Paul Roos, Larissa Frohnapfel, Steve Quiros, Florian Ringel, Bernd Kaina
Glioblastoma is the most frequent and aggressive form of high-grade malignant glioma. Due to the dismal prognosis faced by patients suffering from this disease, there is a need for identifying new targets that might improve therapy. The aim of this study was to determine the contribution of the DNA double-strand break (DSB) repair protein X-ray repair cross-complementing 3 (XRCC3) to the resistance of glioma cells to the chemotherapeutic drug temozolomide. Analysis of a publicly available database, E-GEOD-4290, showed that gliomas overexpress XRCC3 (NM_005432) compared to normal brain tissue...
March 21, 2018: Cancer Letters
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