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https://www.readbyqxmd.com/read/27783662/mertk-inhibition-induces-polyploidy-and-promotes-cell-death-and-cellular-senescence-in-glioblastoma-multiforme
#1
Alexandra Sufit, Alisa B Lee-Sherick, Deborah DeRyckere, Manali Rupji, Bhakti Dwivedi, Marileila Varella-Garcia, Angela M Pierce, Jeanne Kowalski, Xiaodong Wang, Stephen V Frye, H Shelton Earp, Amy K Keating, Douglas K Graham
BACKGROUND: MER receptor tyrosine kinase (MERTK) is expressed in a variety of malignancies, including glioblastoma multiforme (GBM). Our previous work demonstrated that inhibition of MERTK using RNA interference induced cell death and chemosensitivity in GBM cells, implicating MERTK as a potential therapeutic target. Here we investigate whether a novel MERTK-selective small molecule tyrosine kinase inhibitor, UNC2025, has similar anti-tumor effects in GBM cell lines. METHODS: Correlations between expression of GAS6, a MERTK ligand, and prognosis were determined using data from the TCGA database...
2016: PloS One
https://www.readbyqxmd.com/read/27217440/braf-status-in-personalizing-treatment-approaches-for-pediatric-gliomas
#2
Aleksandra Olow, Sabine Mueller, Xiaodong Yang, Rintaro Hashizume, Justin Meyerowitz, William Weiss, Adam C Resnick, Angela J Waanders, Lukas J A Stalpers, Mitchel S Berger, Nalin Gupta, C David James, Claudia K Petritsch, Daphne A Haas-Kogan
PURPOSE: Alteration of the BRAF/MEK/MAPK pathway is the hallmark of pediatric low-grade gliomas (PLGGs), and mTOR activation has been documented in the majority of these tumors. We investigated combinations of MEK1/2, BRAF(V600E) and mTOR inhibitors in gliomas carrying specific genetic alterations of the MAPK pathway. EXPERIMENTAL DESIGN: We used human glioma lines containing BRAF(V600E) (adult high-grade: AM-38, DBTRG, PLGG: BT40), or wild-type BRAF (pediatric high-grade: SF188, SF9427, SF8628) and isogenic systems of KIAA1549:BRAF-expressing NIH/3T3 cells and BRAF(V600E)-expressing murine brain cells...
November 1, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27095947/the-histone-deacetylase-inhibitor-pci-24781-as-a-putative-radiosensitizer-in-pediatric-glioblastoma-cell-lines
#3
Pamela Viani de Andrade, Augusto Faria Andrade, Rosane Gomes de Paula Queiroz, Carlos Alberto Scrideli, Luiz Gonzaga Tone, Elvis Terci Valera
BACKGROUND: Glioblastoma (GBM) is considered to be one of the most aggressive tumors of the central nervous system (CNS). Even with the use of modern treatment protocols, the prognosis remains reserved, with children with GBM having a mean survival of 12-15 months. METHODS: In the present study we investigated the potential radiosensitizing effect of PCI-24781, a potent pan-histone deacetylase inhibitor (HDACi), on the SF188 and KNS42 cell lines of pediatric GBM...
2016: Cancer Cell International
https://www.readbyqxmd.com/read/26933822/downregulation-of-mir-137-and-mir-6500-3p-promotes-cell-proliferation-in-pediatric-high-grade-gliomas
#4
Muh-Lii Liang, Tsung-Han Hsieh, Kim-Hai Ng, Ya-Ni Tsai, Cheng-Fong Tsai, Meng-En Chao, Da-Jung Liu, Shing-Shiung Chu, Wan Chen, Yun-Ru Liu, Ren-Shyan Liu, Shih-Chieh Lin, Donald Ming-Tak Ho, Tai-Tong Wong, Muh-Hwa Yang, Hsei-Wei Wang
Pediatric high-grade gliomas (pHGGs) are aggressive brain tumors affecting children, and outcomes have remained dismal, even with access to new multimodal therapies. In this study, we compared the miRNomes and transcriptomes of pediatric low- (pLGGs) and high-grade gliomas (pHGGs) using small RNA sequencing (smRNA-Seq) and gene expression microarray, respectively. Through integrated bioinformatics analyses and experimental validation, we identified miR-137 and miR-6500-3p as significantly downregulated in pHGGs...
April 12, 2016: Oncotarget
https://www.readbyqxmd.com/read/25628092/cell-migration-in-paediatric-glioma-characterisation-and-potential-therapeutic-targeting
#5
J V Cockle, S Picton, J Levesley, E Ilett, A M Carcaboso, S Short, L P Steel, A Melcher, S E Lawler, A Brüning-Richardson
BACKGROUND: Paediatric high grade glioma (pHGG) and diffuse intrinsic pontine glioma (DIPG) are highly aggressive brain tumours. Their invasive phenotype contributes to their limited therapeutic response, and novel treatments that block brain tumour invasion are needed. METHODS: Here, we examine the migratory characteristics and treatment effect of small molecule glycogen synthase kinase-3 inhibitors, lithium chloride (LiCl) and the indirubin derivative 6-bromoindirubin-oxime (BIO), previously shown to inhibit the migration of adult glioma cells, on two pHGG cell lines (SF188 and KNS42) and one patient-derived DIPG line (HSJD-DIPG-007) using 2D (transwell membrane, immunofluorescence, live cell imaging) and 3D (migration on nanofibre plates and spheroid invasion in collagen) assays...
February 17, 2015: British Journal of Cancer
https://www.readbyqxmd.com/read/25587330/structural-characterisation-of-a-polysaccharide-from-radix-ranunculus-ternati
#6
Xuefeng Huang, Yun Zhao, Xin Jin
A water soluble polysaccharide, HB-1, with a molecular weight of 23,930, was isolated from radix Ranunculi ternati. by hot water extraction, ethanol precipitation, deproteination,ultrafiltration and gel-filtration column chromatography. Its sugar composition was determined by GLC as Glc, Ara, and Gal in a molar ration of 16.071: 2.722: 1. And the absolute configuration of Glc was identified as D. Smith degradation and methylation reaction showed the proportion of -(1)Glc (A) was about 16%, -(1)Glc(4)- (B) about 62%, (C) about 14%, and -(1)Gal(6)- (D) about 8%...
2014: Iranian Journal of Pharmaceutical Research: IJPR
https://www.readbyqxmd.com/read/25084455/lactate-and-choline-metabolites-detected-in-vitro-by-nuclear-magnetic-resonance-spectroscopy-are-potential-metabolic-biomarkers-for-pi3k-inhibition-in-pediatric-glioblastoma
#7
Nada M S Al-Saffar, Lynley V Marshall, L Elizabeth Jackson, Geetha Balarajah, Thomas R Eykyn, Alice Agliano, Paul A Clarke, Chris Jones, Paul Workman, Andrew D J Pearson, Martin O Leach
The phosphoinositide 3-kinase (PI3K) pathway is believed to be of key importance in pediatric glioblastoma. Novel inhibitors of the PI3K pathway are being developed and are entering clinical trials. Our aim is to identify potential non-invasive biomarkers of PI3K signaling pathway inhibition in pediatric glioblastoma using in vitro nuclear magnetic resonance (NMR) spectroscopy, to aid identification of target inhibition and therapeutic response in early phase clinical trials of PI3K inhibitors in childhood cancer...
2014: PloS One
https://www.readbyqxmd.com/read/23887645/polo-like-kinase-1-inhibition-causes-decreased-proliferation-by-cell-cycle-arrest-leading-to-cell-death-in-glioblastoma
#8
J A Pezuk, M S Brassesco, A G Morales, J C de Oliveira, R G de Paula Queiroz, H R Machado, C G Carlotti, L Neder, C A Scrideli, L G Tone
Glioblastoma (GBM) is one of the most aggressive central nervous system tumors with a patient's median survival of <1 year. Polo-like kinases (PLKs) are a family of serine/threonine kinases that have key roles in cell cycle control and DNA-damage response. We evaluated PLK1, 2, 3 and 4 gene expression in 8 GBM cell lines and 17 tumor samples, and analyzed the effect of the PLK1 inhibition on SF188 and T98G GBM cell lines and 13 primary cultures. Our data showed PLK1 overexpression and a variable altered expression of PLK2, 3 and 4 genes in GBM tumor samples and cell lines...
September 2013: Cancer Gene Therapy
https://www.readbyqxmd.com/read/23728478/bub1-and-bubr1-inhibition-decreases-proliferation-and-colony-formation-and-enhances-radiation-sensitivity-in-pediatric-glioblastoma-cells
#9
Andressa Gois Morales, Julia Alejandra Pezuk, María Sol Brassesco, Jaqueline Carvalho de Oliveira, Rosane Gomes de Paula Queiroz, Hélio Rubens Machado, Carlos Gilberto Carlotti, Luciano Neder, Harley Francisco de Oliveira, Carlos Alberto Scrideli, Luiz Gonzaga Tone
PURPOSE: Glioblastoma (GBM) is a very aggressive and lethal brain tumor with poor prognosis. Despite new treatment strategies, patients' median survival is still lower than 1 year in most cases. The expression of the BUB gene family has demonstrated to be altered in a variety of solid tumors, pointing to a role as putative therapeutic target. The purpose of this study was to determine BUB1, BUB3, and BUBR1 gene expression profiles in glioblastoma and to analyze the effects of BUB1 and BUBR1 inhibition combined or not with Temozolomide and radiation in the pediatric SF188 GBM cell line...
December 2013: Child's Nervous System: ChNS: Official Journal of the International Society for Pediatric Neurosurgery
https://www.readbyqxmd.com/read/23713868/inhibition-of-polo-like-kinase-1-induces-cell-cycle-arrest-and-sensitizes-glioblastoma-cells-to-ionizing-radiation
#10
Julia Alejandra Pezuk, María Sol Brassesco, Andressa Gois Morales, Jaqueline Carvalho de Oliveira, Harley Francisco de Oliveira, Carlos Alberto Scrideli, Luiz Gonzaga Tone
Despite efforts to improve surgical, radiologic, and chemotherapeutic strategies, the outcome of patients with glioblastoma (GBM) is still poor. Polo-like kinase 1 (PLK1) is a serine/threonine kinase that plays key roles in cell cycle control and has been associated with tumor growth and prognosis. Here, we aimed at testing the radiosensitizing effects of the PLK1 inhibitor BI 2536 on eight GBM cell lines. For cell cycle analysis, T98G, U251, U343 MG-a, LN319, SF188, U138 MG, and U87 MG cell lines were treated with 10, 50, or 100 nM of BI 2536 for 24 hours...
September 2013: Cancer Biotherapy & Radiopharmaceuticals
https://www.readbyqxmd.com/read/23691145/abt-263-enhances-sensitivity-to-metformin-and-2-deoxyglucose-in-pediatric-glioma-by-promoting-apoptotic-cell-death
#11
Jane Levesley, Lynette Steele, Claire Taylor, Priyank Sinha, Sean E Lawler
Pediatric high grade glioma is refractory to conventional multimodal treatment, highlighting a need to develop novel efficacious therapies. We investigated tumor metabolism as a potential therapeutic target in a panel of diverse pediatric glioma cell lines (SF188, KNS42, UW479 and RES186) using metformin and 2-deoxyglucose. As a single agent, metformin had little effect on cell viability overall. SF188 cells were highly sensitive to 2-deoxyglucose however, combination of metformin with 2-deoxyglucose significantly reduced cell proliferation compared to either drug alone in all cell lines tested...
2013: PloS One
https://www.readbyqxmd.com/read/23165942/infrasound-sensitizes-human-glioblastoma-cells-to-cisplatin-induced-apoptosis
#12
Kenneth Rachlin, Dan H Moore, Garret Yount
The development of nontoxic agents that can selectively enhance the cytotoxicity of chemotherapy is an important aim in oncology. This study evaluates the ability of infrasound exposure to sensitize glioblastoma cells to cisplatin-induced apoptosis. The infrasound was delivered using a device designed to replicate the unique infrasound emissions measured during external Qigong treatments. Human glioblastoma cell lines harboring wild-type p53 (U87) or mutant p53 (U251, SF210, and SF188) were treated in culture with cisplatin, infrasound emissions, or the combination of the 2 agents...
November 2013: Integrative Cancer Therapies
https://www.readbyqxmd.com/read/23011120/growth-properties-of-sf188-v-human-glioma-in-rats-in-vivo-observed-by-magnetic-resonance-imaging
#13
Rachel Grossman, Betty Tyler, Henry Brem, Charles G Eberhart, Silun Wang, De-Xue Fu, Zhibo Wen, Jinyuan Zhou
SF188/V+ is a highly vascular human glioma model that is based on transfection of vascular endothelial growth factor (VEGF) cDNA into SF188/V- cells. This study aims to assess its growth and vascularity properties in vivo in a rat model. Thirty-two adult rats were inoculated with SF188/V+ tumor cells, and, for comparison, five were inoculated with SF188/V- tumor cells. Several conventional magnetic resonance imaging (MRI) sequences were acquired, and several quantitative structural (T(2) and T(1)), functional [isotropic apparent diffusion coefficient (ADC) and blood flow], and molecular [protein and peptide-based amide proton transfer (APT)] MRI parameters were mapped on a 4...
December 2012: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/22935578/comparative-evaluation-of-18f-labeled-glutamic-acid-and-glutamine-as-tumor-metabolic-imaging-agents
#14
COMPARATIVE STUDY
Karl Ploessl, Limin Wang, Brian P Lieberman, Wenchao Qu, Hank F Kung
UNLABELLED: (18)F-labeled (2S,4R)-4-fluoro-l-glutamine (4F-GLN) has demonstrated high uptake in tumor cells that undergo high growth and proliferation. Similar tumor targeting properties have also been observed for (18)F-labeled (2S,4R)-4-fluoro-l-glutamate (4F-GLU), suggesting that both are useful imaging agents. A new labeling procedure facilitates the preparation of (18)F-(2S,4R)4F-GLN and (18)F-(2S,4R)4F-GLU with confirmed radiochemical and enantiomeric purity. Here, we report the preparation and comparative evaluation of (18)F-(2S,4R)4F-GLN and (18)F-(2S,4R)4F-GLU as tumor metabolic imaging agents...
October 2012: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/22415968/polo-like-kinase-1-inhibition-kills-glioblastoma-multiforme-brain-tumor-cells-in-part-through-loss-of-sox2-and-delays-tumor-progression-in-mice
#15
Cathy Lee, Abbas Fotovati, Joanna Triscott, James Chen, Chitra Venugopal, Ash Singhal, Christopher Dunham, John M Kerr, Maite Verreault, Stephen Yip, Hiroaki Wakimoto, Chris Jones, Aarthi Jayanthan, Aru Narendran, Sheila K Singh, Sandra E Dunn
Glioblastoma multiforme (GBM) ranks among the deadliest types of cancer and given these new therapies are urgently needed. To identify molecular targets, we queried a microarray profiling 467 human GBMs and discovered that polo-like kinase 1 (PLK1) was highly expressed in these tumors and that it clustered with the proliferative subtype. Patients with PLK1-high tumors were more likely to die from their disease suggesting that current therapies are inactive against such tumors. This prompted us to examine its expression in brain tumor initiating cells (BTICs) given their association with treatment failure...
June 2012: Stem Cells
https://www.readbyqxmd.com/read/22173839/preparation-and-characterization-of-l-5-11c-glutamine-for-metabolic-imaging-of-tumors
#16
Wenchao Qu, Shunichi Oya, Brian P Lieberman, Karl Ploessl, Limin Wang, David R Wise, Chaitanya R Divgi, Lewis A Chodosh, Lewis P Chodosh, Craig B Thompson, Hank F Kung
UNLABELLED: Recently, there has been a renewed interest in the study of tumor metabolism above and beyond the Warburg effect. Studies on cancer cell metabolism have provided evidence that tumor-specific activation of signaling pathways, such as the upregulation of the oncogene myc, can regulate glutamine uptake and its metabolism through glutaminolysis to provide the cancer cell with a replacement of energy source. METHODS: We report a convenient procedure to prepare l-[5-(11)C]-glutamine...
January 2012: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/22095958/pet-imaging-of-glutaminolysis-in-tumors-by-18f-2s-4r-4-fluoroglutamine
#17
Brian P Lieberman, Karl Ploessl, Limin Wang, Wenchao Qu, Zhihao Zha, David R Wise, Lewis A Chodosh, George Belka, Craig B Thompson, Hank F Kung
UNLABELLED: Changes in gene expression, metabolism, and energy requirements are hallmarks of cancer growth and self-sufficiency. Upregulation of the PI3K/Akt/mTor pathway in tumor cells has been shown to stimulate aerobic glycolysis, which has enabled (18)F-FDG PET tumor imaging. However, of the millions of (18)F-FDG PET scans conducted per year, a significant number of malignant tumors are (18)F-FDG PET-negative. Recent studies suggest that several tumors may use glutamine as the key nutrient for survival...
December 2011: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/21730024/yb-1-bridges-neural-stem-cells-and-brain-tumor-initiating-cells-via-its-roles-in-differentiation-and-cell-growth
#18
Abbas Fotovati, Samah Abu-Ali, Pei-Shan Wang, Loic P Deleyrolle, Cathy Lee, Joanna Triscott, James Y Chen, Sonia Franciosi, Yasuhiro Nakamura, Yasuo Sugita, Takeshi Uchiumi, Michihiko Kuwano, Blair R Leavitt, Sheila K Singh, Alexa Jury, Chris Jones, Hiroaki Wakimoto, Brent A Reynolds, Catherine J Pallen, Sandra E Dunn
The Y-box binding protein 1 (YB-1) is upregulated in many human malignancies including glioblastoma (GBM). It is also essential for normal brain development, suggesting that YB-1 is part of a neural stem cell (NSC) network. Here, we show that YB-1 was highly expressed in the subventricular zone (SVZ) of mouse fetal brain tissues but not in terminally differentiated primary astrocytes. Conversely, YB-1 knockout mice had reduced Sox-2, nestin, and musashi-1 expression in the SVZ. Although primary murine neurospheres were rich in YB-1, its expression was lost during glial differentiation...
August 15, 2011: Cancer Research
https://www.readbyqxmd.com/read/21692241/inhibition-of-fatty-acid-oxidation-by-etomoxir-impairs-nadph-production-and-increases-reactive-oxygen-species-resulting-in-atp-depletion-and-cell-death-in-human-glioblastoma-cells
#19
Lisa S Pike, Amy L Smift, Nicole J Croteau, David A Ferrick, Min Wu
Normal differentiated cells rely primarily on mitochondrial oxidative phosphorylation to produce adenosine triphosphate (ATP) to maintain their viability and functions by using three major bioenergetic fuels: glucose, glutamine and fatty acids. Many cancer cells, however, rely on aerobic glycolysis for their growth and survival, and recent studies indicate that some cancer cells depend on glutamine as well. This altered metabolism in cancers occurs through oncogene activation or loss of tumor suppressor genes in multiple signaling pathways, including the phosphoinositide 3-kinase and Myc pathways...
June 2011: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/21658976/facile-synthesis-5-13-c-4-2-h-2-l-glutamine-for-hyperpolarized-mrs-imaging-of-cancer-cell-metabolism
#20
Wenchao Qu, Zhihao Zha, Brian P Lieberman, Anthony Mancuso, Mathew Stetz, Rahim Rizzi, Karl Ploessl, David Wise, Craig Thompson, Hank F Kung
RATIONALE AND OBJECTIVES: Recent reports suggest that cancer cells may use glutamine, instead of glucose, as an alternative source of metabolic energy. This suggests that hyperpolarized (13)C glutamine may be useful as a magnetic resonance spectroscopy (MRS) imaging agent for detecting changes in glutamine metabolism in cancerous cells or tissues. MATERIALS AND METHODS: Synthesis of [5-(13)C-4-(2)H(2)]-L-glutamine was accomplished through a seven-step synthetic pathway with a 44% overall yield...
August 2011: Academic Radiology
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