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https://www.readbyqxmd.com/read/28342984/hdac4-and-hdac6-sustain-dna-double-strand-break-repair-and-stem-like-phenotype-by-promoting-radioresistance-in-glioblastoma-cells
#1
Francesco Marampon, Francesca Megiorni, Simona Camero, Clara Crescioli, Heather P McDowell, Roberta Sferra, Antonella Vetuschi, Simona Pompili, Luca Ventura, Francesca De Felice, Vincenzo Tombolini, Carlo Dominici, Roberto Maggio, Claudio Festuccia, Giovanni Luca Gravina
The role of histone deacetylase (HDAC) 4 and 6 in glioblastoma (GBM) radioresistance was investigated. We found that tumor samples from 31 GBM patients, who underwent temozolomide and radiotherapy combined treatment, showed HDAC4 and HDAC6 expression in 93.5% and 96.7% of cases, respectively. Retrospective clinical data analysis demonstrated that high-intensity HDAC4 and/or HDAC6 immunostaining was predictive of poor clinical outcome. In vitro experiments revealed that short hairpin RNA-mediated silencing of HDAC4 or HDAC6 radiosensitized U87MG and U251MG GBM cell lines by promoting DNA double-strand break (DSBs) accumulation and by affecting DSBs repair molecular machinery...
March 22, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28341197/label-free-quantitative-proteomics-unravels-the-importance-of-rna-processing-in-glioma-malignancy
#2
Baibin Bi, Feng Li, Jisheng Guo, Cuiling Li, Ruirui Jing, Xin Lv, Xinjun Chen, Fengqin Wang, Kazem M Azadzoi, Lin Wang, Yuguang Liu, Jing-Hua Yang
Glioma, one of the most common cancers in human, is classified to different grades according to the degrees of malignancy. Glioblastoma (GBM) is known to be the most malignant (Grade IV) whereas low-grade astrocytoma (LGA, Grade II) is relatively benign. The mechanism underlying the pathogenesis and progression of glioma malignancy remains unclear. Here we report a quantitative proteomic study to elucidate the differences between GBM and LGA using liquid chromatography and tandem mass spectrometry followed by label-free quantification...
March 21, 2017: Neuroscience
https://www.readbyqxmd.com/read/28339964/treatment-strategy-and-idh-status-improve-nomogram-validity-in-newly-diagnosed-gbm-patients
#3
Wen Cheng, Chuanbao Zhang, Xiufang Ren, Zheng Wang, Xing Liu, Sheng Han, Anhua Wu
No abstract text is available yet for this article.
March 3, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/28339833/vdac1-is-a-molecular-target-in-glioblastoma-with-its-depletion-leading-to-reprogrammed-metabolism-and-reversed-oncogenic-properties
#4
Tasleem Arif, Yakov Kerlin, Itay Nakdimon, Daniel Benharroch, Avijit Paul, Daniela Dadon-Klein, Varda Shoshan-Barmatz
Background.: Glioblastoma (GBM), an aggressive brain tumor with frequent relapses and a high mortality, still awaits an effective treatment. Like many cancers, GBM cells acquire oncogenic properties, including metabolic reprogramming, vital for growth. As such, tumor metabolism is an emerging avenue for cancer therapy. One relevant target is the voltage-dependent anion channel 1 (VDAC1), a mitochondrial protein controlling cell energy and metabolic homeostasis. Methods...
February 28, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/28339723/leveraging-molecular-datasets-for-biomarker-based-clinical-trial-design-in-glioblastoma
#5
Shyam K Tanguturi, Lorenzo Trippa, Shakti H Ramkissoon, Kristine Pelton, David Knoff, David Sandak, Neal I Lindeman, Azra H Ligon, Rameen Beroukhim, Giovanni Parmigiani, Patrick Y Wen, Keith L Ligon, Brian M Alexander
Background.: Biomarkers can improve clinical trial efficiency, but designing and interpreting biomarker-driven trials require knowledge of relationships among biomarkers, clinical covariates, and endpoints. We investigated these relationships across genomic subgroups of glioblastoma (GBM) within our institution (DF/BWCC), validated results in The Cancer Genome Atlas (TCGA), and demonstrated potential impacts on clinical trial design and interpretation. Methods.: We identified genotyped patients at DF/BWCC, and clinical associations across 4 common GBM genomic biomarker groups were compared along with overall survival (OS), progression-free survival (PFS), and survival post-progression (SPP)...
February 20, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/28337377/the-e3-ubiquitin-ligase-chip-mir-92b-pten-regulatory-network-contributes-to-tumorigenesis-of-glioblastoma
#6
Tao Xu, Hongxiang Wang, Mei Jiang, Yong Yan, Weiqing Li, Hanchong Xu, Qilin Huang, Yicheng Lu, Juxiang Chen
Glioblastoma (GBM) is the most frequent, aggressive and fatal tumor in the central nervous system, while PTEN signaling is frequently deregulated in human GBM. We previously reported the up-regulation of the carboxyl terminal of Hsp70-interacting protein (CHIP) in GBM, however, the causal link between its dysregulation and tumorigenesis has not been established. Using miRNA microarrays and quantitative RT-PCR (qRT-PCR), we found activation of CHIP leads to increased transcription of miR-92b. Further studies in T98G and LN229 cells showed overexpression of miR-92b elicited reduction of PTEN and efficiently rescued glioma development in CHIP knock-down cells...
2017: American Journal of Cancer Research
https://www.readbyqxmd.com/read/28336765/mir-330-5p-suppresses-glioblastoma-cell-proliferation-and-invasiveness-through-targeting-itga5
#7
Linsen Feng, Jianhua Ma, Jing Ji, Haiming Ji, Yichun Liu, Weixing Hu
The present study intended to investigate the biological effects of miR-330-5p on glioblastoma (GBM) cell proliferation and invasiveness by targeting ITGA5. The expressions of miR-330-5p and ITGA5 mRNA in GBM cell lines (U87, U251 and U373) and normal brain glial cell line (HEB) were detected using RT-qPCR. Protein expression of ITGA5 was examined using Western blot.  This study used MTT assay, colony formation assay, Transwell assay, wound healing assay and flow cytometry analysis in order to determine the biological functions of GBM cells (including cell proliferation, invasion, migration, apoptosis and cell cycle)...
March 23, 2017: Bioscience Reports
https://www.readbyqxmd.com/read/28333248/the-evolutionary-dynamics-of-orthologs-that-shift-in-gene-body-methylation-between-arabidopsis-species
#8
Shohei Takuno, Danelle K Seymour, Brandon S Gaut
DNA methylation labels a specific subset of genes in plant genomes. Recent work has shown that this gene-body methylation (gbM) is a conserved feature of orthologs, because highly methylated genes in one species tend to be highly methylated in another. In this study, we examined the exceptions to that rule by identifying genes that differ in gbM status between two plant species - Arabidopsis thaliana and Arabidopsis lyrata. Using Capsella grandiflora as an outgroup, we polarized the loss and gain of gbM for orthologs in Arabidopsis lineages...
March 2, 2017: Molecular Biology and Evolution
https://www.readbyqxmd.com/read/28332095/identification-of-t-cell-target-antigens-in-glioblastoma-stem-like-cells-using-an-integrated-proteomics-based-approach-in-patient-specimens
#9
Carmen Rapp, Rolf Warta, Slava Stamova, Ali Nowrouzi, Christoph Geisenberger, Zoltan Gal, Saskia Roesch, Steffen Dettling, Simone Juenger, Mariana Bucur, Christine Jungk, Philip DaoTrong, Rezvan Ahmadi, Felix Sahm, David Reuss, Valentina Fermi, Esther Herpel, Volker Eckstein, Niels Grabe, Christoph Schramm, Markus A Weigand, Juergen Debus, Andreas von Deimling, Andreas Unterberg, Amir Abdollahi, Philipp Beckhove, Christel Herold-Mende
Glioblastoma (GBM) is a highly aggressive brain tumor and still remains incurable. Among others, an immature subpopulation of self-renewing and therapy-resistant tumor cells-often referred to as glioblastoma stem-like cells (GSCs)-has been shown to contribute to disease recurrence. To target these cells personalized immunotherapy has gained a lot of interest, e.g. by reactivating pre-existing anti-tumor immune responses against GSC antigens. To identify T cell targets commonly presented by GSCs and their differentiated counterpart, we used a proteomics-based separation of GSC proteins in combination with a T cell activation assay...
March 22, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28332000/neutrophil-lymphocyte-ratio-dynamics-during-concurrent-chemo-radiotherapy-for-glioblastoma-is-an-independent-predictor-for-overall-survival
#10
Matthew Mason, Catherine Maurice, Mairead G McNamara, Minh Thi Tieu, Zarnie Lwin, Barbara-Ann Millar, Cynthia Menard, Normand Laperriere, Michael Milosevic, Eshetu G Atenafu, Warren Mason, Caroline Chung
Elevated neutrophil-lymphocyte ratio (NLR) may predict worse outcomes in cancer, including glioblastoma (GBM). This study assessed whether change in NLR during focal radiotherapy and concomitant temozolomide (RT-TMZ) provides further prognostic information. This was a retrospective review of patients treated with RT-TMZ for histologically confirmed GBM from January 2004 to September 2010. Variables assessed included age, ECOG performance status (PS), dexamethasone use and extent of surgery. Hematological results were collected at baseline, during and 4 weeks post RT-TMZ...
March 22, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28327992/cyst-fluid-from-cystic-malignant-brain-tumors-a-reservoir-of-nutrients-including-growth-factor-like-nutrients-for-tumor-cells
#11
Daniel Dahlberg, Eduard A Struys, Erwin E Jansen, Lars Mørkrid, Øivind Midttun, Bjørnar Hassel
BACKGROUND: Brain tumors may have cysts, whose content of nutrients could influence tumor cell microenvironment and growth. OBJECTIVE: To measure nutrients in cyst fluid from glioblastoma multiforme (GBM) and metastatic brain tumors. METHODS: Quantification of nutrients in cyst fluid from 12 to 18 GBMs and 4 to 10 metastatic brain tumors. RESULTS: GBM cysts contained glucose at 2.2 mmol/L (median value; range <0.8-3...
January 25, 2017: Neurosurgery
https://www.readbyqxmd.com/read/28327577/metabolic-profiling-of-idh-mutation-and-malignant-progression-in-infiltrating-glioma
#12
Llewellyn E Jalbert, Adam Elkhaled, Joanna J Phillips, Evan Neill, Aurelia Williams, Jason C Crane, Marram P Olson, Annette M Molinaro, Mitchel S Berger, John Kurhanewicz, Sabrina M Ronen, Susan M Chang, Sarah J Nelson
Infiltrating low grade gliomas (LGGs) are heterogeneous in their behavior and the strategies used for clinical management are highly variable. A key factor in clinical decision-making is that patients with mutations in the isocitrate dehydrogenase 1 and 2 (IDH1/2) oncogenes are more likely to have a favorable outcome and be sensitive to treatment. Because of their relatively long overall median survival, more aggressive treatments are typically reserved for patients that have undergone malignant progression (MP) to an anaplastic glioma or secondary glioblastoma (GBM)...
March 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28327358/a-cell-autonomous-positive-signaling-circuit-associated-with-the-pdgf-no-id4-regulatory-axis-in-glioblastoma-cells
#13
Kiyoung Eun, Hye-Min Jeon, Sung-Ok Kim, Sang-Hun Choi, Seon Yong Lee, Xiong Jin, Sung-Chan Kim, Hyunggee Kim
Most cancer-related signaling pathways sustain their active or inactive status via genetic mutations or various regulatory mechanisms. Previously, we demonstrated that platelet-derived growth factor (PDGF) activates Notch signaling through nitric oxide (NO)-signaling-driven activation of inhibitor of differentiation 4 (ID4) in glioblastoma (GBM) stem cells (GSCs) and endothelial cells in the vascular niche of GBM, leading to maintenance of GSC traits and GBM progression. Here, we determined that the PDGF-NO-ID4-signaling axis is constantly activated through a positive regulatory circuit...
March 18, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28325770/high-risk-sexual-behaviours-among-gay-and-bisexual-men-comparing-event-level-casual-sex-encounters-among-seroconverters-and-non-seroconverters
#14
Ian Down, Jeanne Ellard, Kathy Triffitt, Iryna Zablotska, Michael Hurley, Graham Brown, Jack Bradley, Garrett Prestage
BACKGROUND: With increasing use of non-condom-based HIV risk reduction strategies by gay and bisexual men (GBM), we compared occasions of condomless anal intercourse with casual partners (CLAIC) that resulted in HIV transmission and similar occasions when HIV transmission did not occur. METHODS: We compared two demographically similar samples of Australian GBM. The HIV Seroconversion Study (SCS) was an online cross-sectional survey of GBM recently diagnosed with HIV...
March 21, 2017: Sexually Transmitted Infections
https://www.readbyqxmd.com/read/28325002/radiomic-analysis-of-multi-contrast-brain-mri-for-the-prediction-of-survival-in-patients-with-glioblastoma-multiforme
#15
Ahmad Chaddad, Christian Desrosiers, Matthew Toews
Image texture features are effective at characterizing the microstructure of cancerous tissues. This paper proposes predicting the survival times of glioblastoma multiforme (GBM) patients using texture features extracted in multi-contrast brain MRI images. Texture features are derived locally from contrast enhancement, necrosis and edema regions in T1-weighted post-contrast and fluid-attenuated inversion-recovery (FLAIR) MRIs, based on the gray-level co-occurrence matrix representation. A statistical analysis based on the Kaplan-Meier method and log-rank test is used to identify the texture features related with the overall survival of GBM patients...
August 2016: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
https://www.readbyqxmd.com/read/28324583/revisiting-cdk-inhibitors-for-treatment-of-glioblastoma-multiforme
#16
REVIEW
Dorota Lubanska, Lisa Porter
Despite extensive efforts and continual progress in research and medicine, outcomes for patients with high-grade glioma remain exceptionally poor. Over the past decade, research has revealed a great deal about the complex biology behind glioma development, and has brought to light some of the major barriers preventing successful treatment. Glioblastoma multiforme (GBM) (stage 4 astrocytoma) is a highly dynamic tumour and one of the most extreme examples of intratumoural heterogeneity, making targeting with specific therapeutics an inefficient and highly unpredictable goal...
March 21, 2017: Drugs in R&D
https://www.readbyqxmd.com/read/28323865/the-microrna-302b-inhibited-insulin-like-growth-factor-binding-protein-2-signaling-pathway-induces-glioma-cell-apoptosis-by-targeting-nuclear-factor-ia
#17
Chin-Cheng Lee, Peng-Hsu Chen, Kuo-Hao Ho, Chwen-Ming Shih, Chia-Hsiung Cheng, Cheng-Wei Lin, Kur-Ta Cheng, Ann-Jeng Liu, Ku-Chung Chen
MicroRNAs are small noncoding RNAs that post-transcriptionally control the expression of genes involved in glioblastoma multiforme (GBM) development. Although miR-302b functions as a tumor suppressor, its role in GBM is still unclear. Therefore, this study comprehensively explored the roles of miR-302b-mediated gene networks in GBM cell death. We found that miR-302b levels were significantly higher in primary astrocytes than in GBM cell lines. miR-302b overexpression dose dependently reduced U87-MG cell viability and induced apoptosis through caspase-3 activation and poly(ADP ribose) polymerase degradation...
2017: PloS One
https://www.readbyqxmd.com/read/28323757/the-performance-of-human-papillomavirus-biomarkers-in-predicting-anal-high-grade-squamous-intraepithelial-lesions-in-gay-and-bisexual-men
#18
Fengyi Jin, Jennifer M Roberts, Andrew E Grulich, I Mary Poynten, Dorothy A Machalek, Alyssa Cornall, Samuel Phillips, Deborah Ekman, Ross L Mcdonald, Richard J Hillman, David J Templeton, Annabelle Farnsworth, Suzanne M Garland, Christopher K Fairley, Sepehr N Tabrizi
BACKGROUND: We evaluate the performance of human papillomavirus (HPV) biomarkers in prediction of anal histological high-grade squamous intraepithelial lesions (HSIL) in gay and bisexual men (GBM) in Sydney, Australia. DESIGN: Baseline analysis of a three-year cohort study METHODS:: The Study of the Prevention of Anal Cancer (SPANC) is natural history study of anal HPV infection in GBM aged ≥35 years. All participants completed cytological and histological assessments...
March 18, 2017: AIDS
https://www.readbyqxmd.com/read/28322833/treatment-of-novel-il17a-inhibitor-in-glioblastoma-implementing-3rd-generation-co-culture-cell-line-and-patient-derived-tumor-model
#19
Md Shamsuddin Sultan Khan, Muhammad Asif, Mohammed Khadeer Ahamed Basheer, Cheng Wei Kang, Fouad Saleh Al-Suede, Oon Chern Ein, Jing Tang, Aman Shah Abdul Majid, Amin Malik Shah Abdul Majid
Despite many treatment options, cancer remains a growing problem and has become the second leading cause of death globally. Here, we present fluorescence molecular tomography (FMT) data regarding the reversion of third generation co-cultured U87+DBTRG and patient-derived GBM tumor model after treatment with novel IL17A inhibitor named FLVM and FLVZ (organic derivatives of caffeic acid). FMT was used to determine tumor angiogenesis volume (assessment of number of blood vessel; the expression of angiogenic factors CD34 and other angiogenic cancer bio-markers) in U87+DBTRG and patient-derived gliomas...
March 18, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28321691/patient-specific-resection-strategy-of-glioblastoma-multiforme-choice-based-on-a-preoperative-scoring-scale
#20
Haihui Jiang, Yong Cui, Xiang Liu, Xiaohui Ren, Song Lin
BACKGROUND: The real association between extent of resection and outcome in patients with glioblastoma multiforme (GBM) remains unclear. OBJECTIVE: The goal of this study was to disclose the effect of gross total resection on survival and establish a scale used for surgical decision making. METHODS: A retrospective review was undertaken of 416 patients who received operation for GBM from 2008 to 2015 in Beijing Tiantan Hospital. To reduce bias in patient selection, propensity score analysis was conducted and 99 pairs of matched GBMs were generated...
March 20, 2017: Annals of Surgical Oncology
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