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Yuan Ren, Nan Ji, Xixiong Kang, Renzhi Wang, Wenbin Ma, Zhenjun Hu, Xingfeng Liu, Yajie Wang
Glioblastoma is a highly vascularized brain tumor that causes high mortality. Kininogen-1 (KNG1) has demonstrated both tumor suppressor and antiangiogenesis properties in gliobastoma cells. We analyzed the microarray and proteomic profiles of tumor tissues from glioblastoma patients (N = 180), and identified potential RNA regulators of the KNG1. Validation experiments in U87 glioblastoma cells showed that the regulation of KNG1 by CTU1, KIAA1274, and RAX was mediated by miR-138. The siRNA-mediated knockdown of CTU1, KIAA1274, or RAX in U87 cells and immortalized human endothelial cells (iHECs) significantly reduced KNG1 expression (P < 0...
October 14, 2016: Oncotarget
Estelle Willems, Arnaud Lombard, Matthias Dedobbeleer, Nicolas Goffart, Bernard Rogister
The main obstacle for the cure of glioblastoma (GBM) is systematic tumor recurrence after treatment. More than 90 % of GBM tumors are indeed recurrent within 5 years after diagnosis and treatment. We urgently need new therapies to specifically address these deadly relapses. A major advance in the understanding of GBM recurrence is the identification of GBM-Initiating Cells (GIC), characterized by their abilities for self-renewal, multilineage differentiation, and proliferation. It appears that these features of GIC could be modulated by the mitotic kinase Aurora A (AurA)...
August 29, 2016: Targeted Oncology
Tuva R Hope, Nathan S White, Joshua Kuperman, Ying Chao, Ghiam Yamin, Hauke Bartch, Natalie M Schenker-Ahmed, Rebecca Rakow-Penner, Robert Bussell, Natsuko Nomura, Santosh Kesari, Atle Bjørnerud, Anders M Dale
The diffusion-weighted magnetic resonance imaging (DWI) technique enables quantification of water mobility for probing microstructural properties of biological tissue and has become an effective tool for collecting information about the underlying pathology of cancerous tissue. Measurements using multiple b-values have indicated biexponential signal attenuation, ascribed to "fast" (high ADC) and "slow" (low ADC) diffusion components. In this empirical study, we investigate the properties of the diffusion time (Δ)-dependent components of the diffusion-weighted (DW) signal in a constant b-value experiment...
2016: Frontiers in Oncology
Luis Tobalina, Jon Pey, Alberto Rezola, Francisco J Planes
MOTIVATION: Gene Essentiality Analysis based on Flux Balance Analysis (FBA-based GEA) is a promising tool for the identification of novel metabolic therapeutic targets in cancer. The reconstruction of cancer-specific metabolic networks, typically based on gene expression data, constitutes a sensible step in this approach. However, to our knowledge, no extensive assessment on the influence of the reconstruction process on the obtained results has been carried out to date. RESULTS: In this article, we aim to study context-specific networks and their FBA-based GEA results for the identification of cancer-specific metabolic essential genes...
2016: PloS One
Mariela C Coccé, Balca R Mardin, Susanne Bens, Adrian M Stütz, Fabiana Lubieniecki, Inga Vater, Jan O Korbel, Reiner Siebert, Cristina N Alonso, Marta S Gallego
Congenital gliobastoma multiforme (GBM) is rare and little is known about the molecular defects underlying the initiation and progression of this tumor type. We present a case of congenital GBM analyzed by conventional cytogenetics, fluorescence in situ hybridization, array comparative genomic hybridization and next generation sequencing. On cytogenetic analysis we detected a reciprocal translocation t(6;12)(q21;q24.3). By sequencing, the translocation was shown to form a fusion between the 5' region of ZCCHC8 and the 3' region of ROS1...
September 2016: Genes, Chromosomes & Cancer
Grazia Maugeri, Agata Grazia D'Amico, Rita Reitano, Salvatore Saccone, Concetta Federico, Sebastiano Cavallaro, Velia D'Agata
Mutation of the Parkin gene causes an autosomal recessive juvenile-onset form of Parkinson's disease. However, recently, it has been also linked to a wide variety of malignancies, including glioblastoma multiforme (GBM). In this pathology, Parkin exhibits a tumor suppressor role by mitigating the proliferation rate in both in vitro and in vivo models. However, Parkin involvement in the hypoxic process has not as yet been investigated. GBM is the most common and aggressive primary brain tumor in adults and is characterized by hypoxic areas...
June 2016: Cell and Tissue Research
Victor Kuete, Louis P Sandjo, Armelle T Mbaveng, Maen Zeino, Thomas Efferth
INTRODUCTION: Multidrug resistance (MDR) in cancer represent a major hurdle in chemotherapy. Previously, the methanol extract of the medicinal spice Xylopia aethiopica displayed considerable cytotoxicity against multidrug resistant (MDR) cancer cell lines. METHODS: The present study was designed to assess the cytotoxicity of compounds, 16α-hydroxy-ent-kauran-19-oic acid (2), 3,4',5-trihydroxy-6″,6″-dimethylpyrano[2,3-g]flavone (3), isotetrandrine (5) and trans-tiliroside (6) derived from the methanol crude extract of Xylopia aethiopica against 9 drug-sensitive and -resistant cancer cell lines...
December 15, 2015: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
Victor Kuete, Hugues Fouotsa, Armelle T Mbaveng, Benjamin Wiench, Augustin E Nkengfack, Thomas Efferth
INTRODUCTION: Chemotherapy is one of the preferred mode of treatment of malignancies, but is complicated by the expression of diverse resistance mechanisms of cancer cells. METHODS: In the present study, we investigated the cytotoxicity of five alkaloids including a furoquinoline montrofoline (1) and four acridones namely 1-hydroxy-4-methoxy-10-methylacridone (2), norevoxanthine (3), evoxanthine (4), 1,3-dimethoxy-10-methylacridone (5) against 9 drug-sensitive and multidrug-resistant (MDR) cancer cell lines...
September 15, 2015: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
Alfonso Caiazzo, Ignacio Ramis-Conde
Palisades are characteristic tissue aberrations that arise in glioblastomas. Observation of palisades is considered as a clinical indicator of the transition from a noninvasive to an invasive tumour. In this paper we propose a computational model to study the influence of the hypoxic switch in palisade formation. For this we produced three-dimensional realistic simulations, based on a multiscale hybrid model, coupling the evolution of tumour cells and the oxygen diffusion in tissue, that depict the shape of palisades during its formation...
October 21, 2015: Journal of Theoretical Biology
Abhishek Ray, Sunil Manjila, Alia M Hdeib, Archana Radhakrishnan, Charles J Nock, Mark L Cohen, Andrew E Sloan
Glioblastoma (GBM) is the most common and the most malignant primary brain tumor in adults, accounting for ~12-15% of all intracranial neoplasms. Despite advances in surgical, medical and radiation therapies, the mortality of GBM remains high, with a median survival ranging between 40 and 70 weeks. Similar to other primary brain tumors, the extracranial metastasis of GBM is extremely rare, occurring in <2% of patients. To demonstrate the clinical characteristics of this rare tumor, we herein present three cases of extracranial GBM metastasis: One to the lungs, which represents the longest reported survival of lung metastases from GBM to date; the second to the soft tissue of the posterior neck; and the third to the lumbar intradural space...
May 2015: Molecular and Clinical Oncology
Victor Kuete, Arno R Nanfack Donfack, Armelle T Mbaveng, Maen Zeino, Pierre Tane, Thomas Efferth
INTRODUCTION: Multidrug resistance in cancer represents a major problem in chemotherapy. The present study was designed to assess the cytotoxicity of anthraquinones from Pentas schimperi, namely damnacanthal (1), damnacanthol (2), 3-hydroxy-2-hydroxymethyl anthraquinone (3) and schimperiquinone B (4) against nine drug-sensitive and multidrug resistant (MDR) cancer cell lines. METHODS: The resazurin reduction assay was used to evaluate the cytotoxicity of the above compounds, whilst caspase-Glo assay was used to detect the activation of caspases enzymes by compounds 1 and 2...
August 2015: Investigational New Drugs
Annelise Letourneur, Simon Roussel, Myriam Bernaudin, Fabien Fillesoye, Jérôme Toutain, Eric T MacKenzie, Edwige Petit, Omar Touzani, Samuel Valable
Glioblastoma is the most aggressive brain tumor and is almost always fatal. These tumors are highly vascularized and angiogenesis is one of the pre-eminent mechanisms underlying their growth. Chronic arterial hypertension (CAH) is a common and worldwide pathology that markedlly alters the structure and function of the vasculature. Yet, essential hypertension is associated in the brain with potential locally impaired vasoreactivity, disturbed perfusion supply and hypoxia phenomena. Even though CAH is a global burden and has an important impact on brain function, nothing is known about the way this frequent pathology would interact with the evolution of glioma...
November 2015: Hypertension Research: Official Journal of the Japanese Society of Hypertension
Barbara Heidenreich, P Sivaramakrishna Rachakonda, Ismail Hosen, Florian Volz, Kari Hemminki, Astrid Weyerbrock, Rajiv Kumar
In this report on 303 gliomas we show the highest frequency of TERT promoter mutations in gliobastomas (80%) followed by oligodendrogliomas (70%) and astrocytomas (39%). We observed positive association between TERT promoter and IDH mutations in oligodendroglial tumors (OR = 26.3; 95% CI 2.5-250.2) and inverse association in primary glioblastomas (OR = 0.13; 95% CI 0.03-0.58). Tumors with TERT promoter mutations compared to those without showed increased TERT transcription; we also showed difference in the transcription levels due to the two main mutations...
April 30, 2015: Oncotarget
Eunice Dotse, Yuhong Bian
This study is aimed at isolating colorectal cancer stem-like cells in vitro using a neurosphere assay method employed in isolating gliobastoma multiforme tumor cells. This was followed with confirmation of the isolated cells by flow cytometry, pluripotent genes expression and in vivo tumorigenicity assay. Using this culture assay, stem-like and non-stem-like CRC cells were isolated and expanded in vitro from purchased Balb/c mice induced with CT26 colorectal cancer (CRC) cell line. The procedure includes an initial mechanical dissociation and chemical digestion of tumor tissue and subsequently plating the resulting single cell suspension in serum-free medium (SFM) or serum-containing medium (SCM)...
August 2016: Cytotechnology
Chi Soo Kang, Yunwei Chen, Hyunbeom Lee, Dijie Liu, Xiang Sun, Junghun Kweon, Michael R Lewis, Hyun-Soon Chong
INTRODUCTION: Therapeutic potential of β-emitting cytotoxic radionuclides (90)Y and (177)Lu has been demonstrated in numerous preclinical and clinical trials. A bifunctional chelate that can effectively complex with the radioisotopes is a critical component for molecular targeted radiotherapy (90)Y and (177)Lu. A new bifunctional chelate 5p-C-NETA with a relatively long alkyl spacer between the chelating backbone and the functional unit for conjugation to a tumor targeting moiety was synthesized...
March 2015: Nuclear Medicine and Biology
Oscar Gallego, M Cuatrecasas, M Benavides, P P Segura, A Berrocal, N Erill, A Colomer, M J Quintana, C Balaña, M Gil, A Gallardo, P Murata, A Barnadas
Epidermal growth factor receptor gene (EGFR) alteration is a common feature in most of glioblastoma multiforme (GBM). Robust response of anti-EGFR treatments has been mostly associated with the EGFR deletion mutant variant III (EGFRvIII) and expression of PTEN. We have performed a prospective trial in order to confirm the efficacy of erlotinib treatment in patients with relapsed GBM who expressed EGFRvIII and PTEN. All patients included in the trial were required to be PTEN (+++), EGFR (+++) and EGFRvIII (+++) positives by immunohistochemistry...
January 2014: Journal of Neuro-oncology
Ana I Fernández-Llamazares, Jaume Adan, Francesc Mitjans, Jan Spengler, Fernando Albericio
Cilengitide is an RGD-peptide of sequence cyclo[RGDfNMeV] that was was developed as a highly active and selective ligand for the αvβ3 and αvβ5 integrin receptors. We describe the synthesis of three analogues of this peptide in which the N-Me group has been replaced by N-oligoethylene glycol (N-OEG) chains of increasing size: namely N-OEG2, N-OEG11, and N-OEG23, which are respectively composed of 2, 11, and 23 ethylene oxide monomer units. The different N-OEG cyclopeptides and the original peptide were compared with respect to lipophilicity and biological activity...
January 15, 2014: Bioconjugate Chemistry
E Salzedo, Mdp Cortes, D Melançon, D Tampieri
Myoinositol (Myo) is a not yet well known metabolite detected using short echo time proton magnetic resonance spectroscopy (HMRS). We examined the role of Myo in 26 patients with new diagnosis of brain lesions including tumors, inflammatory and infectious processes. Histological confirmation of the diagnosis was obtained during gross total surgical resection or stereotactic biopsy of the lesions. The highest ratios of Myo/Cr were found in the hemangiopericytoma and meningioma followed by cortical dysplasia, low grade gliomas, gliobastomas, lymphomas, demyelinating lesions and toxoplasmosis...
March 23, 2009: Neuroradiology Journal
Songhua Fan, Yingjie Zhao, Xiaoying Li, Yanli Du, Jingkun Wang, Xiao Song, Fangfang Zhou, Hongyan Chen, Gong Chen, Yao Zhao, Ying Mao, Qing Lan
Dysregulation of the amino acid transporter SLC7A7 is involved in multiple types of cancer including gliobastoma (GBM), the most malignant form of glioma. We hypothesized that SLC7A7 genetic variants may influence glioma risk. To test this hypothesis, we conducted a case-control study in 736 incident glioma cases and 793 cancer-free controls in a Chinese population by genotyping 22 common single nucleotide polymorphisms in SLC7A7. In single-locus analysis, we found an increased risk was associated with the variant genotypes of rs12888930 (adjusted odds ratio [OR] = 1...
September 2013: Experimental Biology and Medicine
Daniel Jakobs, Anne Hage-Hülsmann, Lars Prenner, Christiane Kolb, Dieter Weiser, Hanns Häberlein
OBJECTIVES: While the use of St John's wort extracts as treatment for mild to moderate depression is well established the mode of action is still under investigation. Individual constituents of St John's wort extract were tested for possible effects on the β1 AR density and a subsequent change in downstream signalling in rat C6 glioblastoma cells. METHODS: The effect of compounds from St John's wort extract on the downregulation of β1 -adrenergic receptor-GFP fusion proteins (β1 AR-green fluorescent protein (GFP)) of transfected rat C6 gliobastoma cells (C6-β1 AR-GFP) was investigated by means of confocal laser scanning microscopy (LSM)...
June 2013: Journal of Pharmacy and Pharmacology
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