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https://www.readbyqxmd.com/read/28449309/tumor-targeting-with-an-isodgr-drug-conjugate
#1
Simone Zanella, Simona Angerani, Pina Arianna, Paula López Rivas, Clelia Giannini, Silvia Panzeri, Daniela Arosio, Michele Caruso, Fabio Gasparri, Ivan Fraietta, Clara Albanese, Aurelio Marsiglio, Luca Pignataro, Laura Belvisi, Umberto Piarulli, Cesare Gennari
Here we report the first example of an isoDGR-drug conjugate (2), designed to release paclitaxel selectively within cancer cells expressing integrin αVβ3. Conjugate 2 was synthesized by connecting the isoDGR peptidomimetic 5 with paclitaxel via the lysosomally cleavable Val-Ala dipeptide linker. Conjugate 2 displayed a low nanomolar affinity for the purified integrin αVβ3 receptor (IC50 = 11.0 nM). The tumor targeting ability of conjugate 2 was assessed in vitro in anti-proliferative assays on two isogenic cancer cell lines characterized by different integrin αVβ3 expression: human glioblastoma U87 (αVβ3 +) and U87 β3-KO (αVβ3 -)...
April 27, 2017: Chemistry: a European Journal
https://www.readbyqxmd.com/read/28449234/magnetic-resonance-imaging-and-computed-tomographic-characteristics-of-a-glioma-causing-calvarial-erosion-in-a-dog
#2
Alfredo Recio, Cristian de la Fuente, Martí Pumarola, Yvonne Espada, Sònia Añor
An 8-year-old female Boxer was examined for acute onset of seizures. On magnetic resonance imaging (MRI), an intra-axial mass with imaging features consistent with glioma was observed in the right cerebral hemisphere. A defect in the temporal bone adjacent to the mass was observed. Postmortem computed tomography (CT) confirmed temporal bone osteolysis and necropsy demonstrated a glioblastoma with associated calvarial erosion. Although occasionally described in human medicine, to our knowledge, this is the first description of a brain glioma causing calvarial erosion in a dog...
April 27, 2017: Veterinary Radiology & Ultrasound
https://www.readbyqxmd.com/read/28449039/polyphyllin-i-induces-g2-m-phase-arrest-and-apoptosis-in-u251-human-glioma-cells-via-mitochondrial-dysfunction-and-the-jnk-signaling-pathway
#3
Jiaxin Liu, Yueting Zhang, Li Chen, Fei Yu, Xiaojin Li, Dan Tao, Jianhua Zhao, Shuai Zhou
Glioblastoma is the most aggressive brain tumor, and its prognosis remains poor. Therefore, novel therapeutic strategies are needed for glioma therapy. Polyphyllin I (PPI), a bioactive constituent extracted from Paris polyphylla, was reported to have anti-tumor activity. However, the detailed mechanism for this activity remains unclear. Here, we investigated the inhibitory effects of PPI on glioma cells and its mechanisms in vitro. U251 cells were treated with various concentrations of PPI (2-9 μM) for 24 to 72 h...
April 26, 2017: Acta Biochimica et Biophysica Sinica
https://www.readbyqxmd.com/read/28447277/assessment-of-pd-1-positive-cells-on-initial-and-secondary-resected-tumor-specimens-of-newly-diagnosed-glioblastoma-and-its-implications-on-patient-outcome
#4
Tsubasa Miyazaki, Eiichi Ishikawa, Masahide Matsuda, Hiroyoshi Akutsu, Satoru Osuka, Noriaki Sakamoto, Shingo Takano, Tetsuya Yamamoto, Koji Tsuboi, Akira Matsumura
Glioblastoma (GBM) is the most common type of malignant brain tumor and has a very poor prognosis. Most patients relapse within 12 months despite aggressive treatment and patient outcome after recurrent is extremely worse. This study was designed to clarify the change of the molecular expression, including programmed cell death 1 (PD-1) and PD-ligand 1 (PD-L1), on the initial and secondary resected tumor specimens and to address the influence of these expressions for patient outcome after second surgery of glioblastoma...
April 26, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28447171/prevalence-and-clinicopathological-features-of-h3-3-g34-mutant-high-grade-gliomas-a-retrospective-study-of-411-consecutive-glioma-cases-in-a-single-institution
#5
Koji Yoshimoto, Ryusuke Hatae, Yuhei Sangatsuda, Satoshi O Suzuki, Nobuhiro Hata, Yojiro Akagi, Daisuke Kuga, Murata Hideki, Koji Yamashita, Osamu Togao, Akio Hiwatashi, Toru Iwaki, Masahiro Mizoguchi, Koji Iihara
A recurrent glycine-to-arginine/valine alteration at codon 34 (G34R/V) within H3F3A, a gene that encodes the replication-independent histone variant H3.3, reportedly occurs exclusively in pediatric glioblastomas. However, the clinicopathological and biological significances of this mutation have not been completely elucidated; especially, no such data exist for tumor samples from Japanese patients. We analyzed 411 consecutive glioma cases representing patients of all ages. Our results demonstrated that 14 patients (3...
April 26, 2017: Brain Tumor Pathology
https://www.readbyqxmd.com/read/28446727/bevacizumab-combined-with-chemotherapy-for-glioblastoma-a-meta-analysis-of-randomized-controlled-trials
#6
Shou-Bo Yang, Kai-Di Gao, Tao Jiang, Shu-Jun Cheng, Wen-Bin Li
Bevacizumab, as antibodies, were applied to inhibit tumor angiogenesis by preventing activation of vascular endothelial growth factor receptor. We analyzed four clinical trials, including 607 patients, to investigate the efficacy and safety of bevacizumab when combined with chemotherapy for the treatment of glioblastomas. Results demonstrated that bevacizumab when combined with chemotherapy improved progression-free survival (HR = 0.66; 95% CI 0.56-0.78; p < 0.00001) compared with bevacizumab or chemotherapy alone...
April 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28445981/mir-148a-increases-glioma-cell-migration-and-invasion-by-downregulating-gadd45a-in-human-gliomas-with-idh1-r132h-mutations
#7
Daming Cui, Pandey Sajan, Jinlong Shi, Yiwen Shen, Ke Wang, Xianyu Deng, Lin Zhou, Pingping Hu, Liang Gao
High-grade gliomas are severe tumors with poor prognosis. An R132H mutation in the isocitrate dehydrogenase (IDH1) gene prolongs the life of glioma patients. In this study, we investigated which genes are differentially regulated in IDH1 wild type (IDH1WT) or IDH1 R132H mutation (IDH1R132H) glioblastoma cells. Growth arrest and DNA-damage-inducible protein (GADD45A) was downregulated and microRNA 148a (miR-148a) was upregulated in in IDH1R132H human glioblastomas tissues. The relationship between GADD45A and miR-148a is unknown...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28445977/serglycin-as-a-potential-biomarker-for-glioma-association-of-serglycin-expression-extent-of-mast-cell-recruitment-and-glioblastoma-progression
#8
Ananya Roy, Sanaz Attarha, Holger Weishaupt, Per-Henrik Edqvist, Fredrik J Swartling, Michael Bergqvist, Florian A Siebzehnrubl, Anja Smits, Fredrik Pontén, Elena Tchougounova
Serglycin is an intracellular proteoglycan with a unique ability to adopt highly divergent structures by glycosylation with variable types of glycosaminoglycans (GAGs) when expressed by different cell types. Serglycin is overexpressed in aggressive cancers suggesting its protumorigenic role. In this study, we explored the expression of serglycin in human glioma and its correlation with survival and immune cell infiltration. We demonstrate that serglycin is expressed in glioma and that increased expression predicts poor survival of patients...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28445974/lowered-expression-of-microrna-125a-5p-in-human-hepatocellular-carcinoma-and-up-regulation-of-its-oncogenic-targets-sirtuin-7-matrix-metalloproteinase-11-and-c-raf
#9
Nicola Coppola, Giorgio de Stefano, Marta Panella, Lorenzo Onorato, Valentina Iodice, Carmine Minichini, Nicola Mosca, Luisa Desiato, Nunzia Farella, Mario Starace, Giulia Liorre, Nicoletta Potenza, Evangelista Sagnelli, Aniello Russo
Human microRNA-125a-5p (miR-125a) is expressed in most tissues where it downregulates the expression of membrane receptors or intracellular transductors of mitogenic signals, thus limiting cell proliferation. Expression of this miRNA generally increases with cell differentiation whereas it is downregulated in several types of tumors, such as breast, lung, ovarian, gastric, colon, and cervical cancers, neuroblastoma, medulloblastoma, glioblastoma, and retinoblastoma. In this study, we focused on hepatocellular carcinoma and used real-time quantitative PCR to measure miR-125a expression in 55 tumor biopsies and in matched adjacent non-tumor liver tissues...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28445970/acid-ceramidase-is-a-novel-drug-target-for-pediatric-brain-tumors
#10
Ninh B Doan, Ha S Nguyen, Andrew Montoure, Mona M Al-Gizawiy, Wade M Mueller, Shekar Kurpad, Scott D Rand, Jennifer M Connelly, Christopher R Chitambar, Kathleen M Schmainda, Shama P Mirza
Pediatric brain tumors are the most common solid tumors in children and are also a leading culprit of cancer-related fatalities in children. Pediatric brain tumors remain hard to treat. In this study, we demonstrated that medulloblastoma, pediatric glioblastoma, and atypical teratoid rhabdoid tumors express significant levels of acid ceramidase, where levels are highest in the radioresistant tumors, suggesting that acid ceramidase may confer radioresistance. More importantly, we also showed that acid ceramidase inhibitors are highly effective at targeting these pediatric brain tumors with low IC50 values (4...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28445937/methylation-mediated-silencing-of-microrna-211-promotes-cell-growth-and-epithelial-to-mesenchymal-transition-through-activation-of-the-akt-%C3%AE-catenin-pathway-in-gbm
#11
Weidong Li, Xiaobo Miao, Lingling Liu, Yue Zhang, Xuejun Jin, Xiaojun Luo, Hai Gao, Xubin Deng
Aberrant expression of miR-211 has frequently been reported in cancer studies; however, its role in glioblastoma multiforme (GBM) has not been examined in detail. We investigated the function and the underlying mechanism of miR-211 in GBM. We revealed that miR-211 was downregulated in GBM tissues and cell lines. Restoration of miR-211 inhibited GBM cell growth and invasion both in vitro and in vivo. The epithelial to mesenchymal transition (EMT) phenotype was reversed when miR-211 expression was restored. HMGA2 was identified as a down-stream target of miR-211...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28445154/role-of-delta-like-4-in-jagged1-induced-tumour-angiogenesis-and-tumour-growth
#12
Chern Ein Oon, Esther Bridges, Helen Sheldon, Richard C A Sainson, Adrian Jubb, Helen Turley, Russell Leek, Francesca Buffa, Adrian L Harris, Ji-Liang Li
Delta-like 4 (DLL4) and Jagged1 (JAG1) are two key Notch ligands implicated in tumour angiogenesis. They were shown to have opposite effects on mouse retinal and adult regenerative angiogenesis. In tumours, both ligands are upregulated but their relative effects and interactions in tumour biology, particularly in tumour response to therapeutic intervention are unclear. Here we demonstrate that DLL4 and JAG1 displayed equal potency in stimulating Notch target genes in HMEC-1 endothelial cells but had opposing effects on sprouting angiogenesis in vitro...
April 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28445150/modulation-of-the-inwardly-rectifying-potassium-channel-kir4-1-by-the-pro-invasive-mir-5096-in-glioblastoma-cells
#13
Dominique Thuringer, Gaetan Chanteloup, Jonathan Boucher, Nicolas Pernet, Christophe Boudesco, Gaetan Jego, Aurelien Chatelier, Patrick Bois, Jessica Gobbo, Laurent Cronier, Eric Solary, Carmen Garrido
Inwardly rectifying potassium channels (Kir), and especially the barium-sensitive Kir4.1 encoded by KCNJ10, are key regulators of glial functions. A lower expression or mislocation of Kir4.1 is detected in human brain tumors. MicroRNAs participate in the regulation of ionic channels and associated neurologic disorders. Here, we analyze effects of miR-5096 on the Kir4.1 expression and function in two glioblastoma cell lines, U87 and U251. Using whole-cell patch-clamp and western-blot analysis, we show that cell loading with miR-5096 decreases the Kir4...
April 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28443460/augmented-expression-of-runx1-deregulates-the-global-gene-expression-of-u87-glioblastoma-multiforme-cells-and-inhibits-tumor-growth-in-mice
#14
Yoel Bogoch, Gilgi Friedlander-Malik, Lior Lupu, Ekaterina Bondar, Nitzan Zohar, Sheila Langier, Zvi Ram, Ido Nachmany, Joseph M Klausner, Niv Pencovich
Glioblastoma multiforme is the most common and aggressive primary brain tumor in adults. A mesenchymal phenotype was associated with tumor aggressiveness and poor prognosis in glioblastoma multiforme patients. Recently, the transcription factor RUNX1 was suggested as a driver of the glioblastoma multiforme mesenchymal gene expression signature; however, its independent role in this process is yet to be described. Here, we assessed the role of RUNX1 in U87 glioblastoma multiforme cells in correspondence to its mediated transcriptome and genome-wide occupancy pattern...
April 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28442265/downregulation-of-%C3%AE-arrestin-1-suppresses-glioblastoma-cell-growth-and-glycolysis-via-inhibition-of-src-signaling
#15
Tian Lan, Haoran Wang, Zhihua Zhang, Mingshan Zhang, Yanming Qu, Zitong Zhao, Xinyi Fan, Qimin Zhan, Yongmei Song, Chunjiang Yu
Glioblastoma multiforme (GBM) is one of the most common brain malignancies worldwide and is typically associated with a dismal prognosis, yet the mechanisms underlying its aggressiveness remain unclear. Here, we revealed that β-arrestin 1 was overexpressed in GBM and contributed to poorer outcome. Knockdown of β-arrestin 1 suppressed the proliferation, invasiveness and glycolysis of GBM cells, and also enhanced temozolomide efficacy. Further, we discovered that knockdown of β-arrestin 1 decreased the activity of Src, and suppression of Src signaling was critically involved in β-arrestin 1 silencing-mediated suppression of GBM malignancies...
April 22, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28441372/assessing-response-of-high-grade-gliomas-to-immune-checkpoint-inhibitors
#16
Solmaz Sahebjam, Dexter G Stallworth, Sepideh Mokhtari, Nam D Tran, John A Arrington
BACKGROUND: Immunotherapeutic agents, especially checkpoint inhibitors, have emerged as the mainstay of therapy for several solid and hematological malignancies. These therapies are under investigation for the treatment of high-grade gliomas and brain metastases. METHODS: This article reviews the unique challenges encountered when evaluating changes on magnetic resonance imaging (MRI) of glioblastomas seen in response to immunotherapy and checkpoint inhibitors and how to effectively incorporate MRI findings into the response assessment of high-grade gliomas to these emerging therapies...
April 2017: Cancer Control: Journal of the Moffitt Cancer Center
https://www.readbyqxmd.com/read/28440504/adipor1-mediated-mir-3908-inhibits-glioblastoma-tumorigenicity-through-downregulation-of-stat2-associated-with-the-ampk-sirt1-pathway
#17
Xiangming Liu, Jinglong Chen, Jinqian Zhang
A prospective method of treatment for cancer is to inhibit oncogene signaling pathways with microRNA (miRNA or miR). In the present study, whether the expression of STAT2, AdipoR1/AMPK/SIRT1 pathway of glioma is regulated by miR-3908 was explored. To confirm whether the predicted miR-3908 is matched with STAT2 and AdipoR1, 3'UTR luciferase activity of STAT2 and AdipoR1 was assessed. In the presence of the mimics or inhibitors of miR-3908, cell function of glioma cells, such as proliferation, growth, migration, invasion and apoptosis were analyzed...
April 20, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28440461/the-role-of-mir-451-in-the-switching-between-proliferation-and-migration-in-malignant-glioma-cells-ampk-signaling-mtor-modulation-and-rac1-activation-required
#18
Kai Zhao, Leilei Wang, Tao Li, Meng Zhu, Chen Zhang, Lei Chen, Pengfei Zhao, Hua Zhou, Shengping Yu, Xuejun Yang
Glioblastoma multiforme (GBM), WHO grade IV astrocytoma, is the most common primary neoplasm of the central nervous system (CNS) and has the highest malignancy and mortality rates. The invasive nature of GBM complicates surgical resection and restricts chemotherapeutic access, contributing to poor patient prognosis. The migration of tumor cells is closely related to the tumor cell proliferation. The acquisition of migratory capability, in addition to intracellular factors, is proposed to be a crucial mechanism during the progression of invasion...
April 21, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28440425/mitochondrial-transcription-factor-a-tfam-is-upregulated-in-glioma
#19
Hyunji Lee, Jisoo Park, Quangdon Tran, Dohoon Kim, Youngeun Hong, Hyeonjeong Cho, So Hee Kwon, Derek Brazil, Seon-Hwan Kim, Jongsun Park
Mitochondrial transcription factor A (TFAM), which was initially discovered as a transcription factor for mitochondrial DNA, has known to be critical for the regulation of mitochondrial DNA. However the possible involvement of TFAM in cancer is largely unknown. In this study, we have provided some evidence that TFAM may have a potential role in brain tumor. Western blot analysis with anti‑TFAM antibody indicated that TFAM is overexpressed in glioblastoma cell lines including U87MG and U251MG. Transcriptome profiling of U87MG and U251MG cells by using deep‑sequencing revealed that TFAM transcripts were upregulated in these cells compared to its of cerebral cortex...
April 12, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28440040/hypofractionated-short-course-radiotherapy-in-elderly-patients-with-glioblastoma-multiforme-an-analysis-of-the-national-cancer-database
#20
Kimberley S Mak, Ankit Agarwal, Muhammad M Qureshi, Minh Tam Truong
For elderly patients with glioblastoma multiforme (GBM), randomized trials have shown similar survival with hypofractionated short-course radiotherapy (SCRT) compared to conventionally fractionated long-course radiotherapy (LCRT). We evaluated the adoption of SCRT along with associated factors and survival in a national patient registry. Using the National Cancer Data Base (NCDB), we identified patients aged ≥70 years with GBM, diagnosed between 1998 and 2011, who received SCRT (34-42 Gy in 2.5-3.4 Gy fractions), or LCRT (58-63 Gy in 1...
April 24, 2017: Cancer Medicine
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