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https://www.readbyqxmd.com/read/29150792/correlation-between-mgmt-promoter-methylation-and-response-to-temozolomide-based-therapy-in-neuroendocrine-neoplasms-an-observational-retrospective-multicenter-study
#1
Davide Campana, Thomas Walter, Sara Pusceddu, Fabio Gelsomino, Emmanuelle Graillot, Natalie Prinzi, Andrea Spallanzani, Michelangelo Fiorentino, Marc Barritault, Filippo Dall'Olio, Nicole Brighi, Guido Biasco
PURPOSE: Temozolomide (TEM) based therapy has been reported being effective in the treatment of metastatic neuroendocrine neoplasms (NEN), with response rates ranging from 30 to 70%. Among patients affected by advanced glioblastoma or melanoma and treated with TEM, loss of tumoral O6-methylguanine DNA methyltransferase (MGMT) is correlated with improved survival. In NEN patients, the role of MGMT deficiency in predicting clinical outcomes of TEM treatment is still under debate. METHODS: In this study we evaluated 95 patients with advanced NENs undergoing treatment with TEM-based therapy...
November 17, 2017: Endocrine
https://www.readbyqxmd.com/read/29150788/ck4-ck6-cyclin-d1-p16-ink4a-and-egfr-expression-in-glioblastoma-with-a-primitive-neuronal-component
#2
Guiyan Xu, Jian Yi Li
Glioblastoma with primitive neuroectodermal tumor-like component (GBM-PNET) is a rare variant of glioblastoma, which was renamed as glioblastoma with a primitive neuronal component (GBM-PN) in new WHO classification of tumours of the central nervous system in 2016. There are few publications on the investigation of GBM-PN. In this study, PCR mRNA arrays on 6 cases of conventional GBM and 10 cases of GBM-PN showed high mRNA level of CDK4 in GBM-PN and low mRNA level of EGFR in GBM-PN. Immunohistochemical stains on tissue microarrays with 28 cases of conventional GBM and 13 cases of GBM-PN demonstrated that CDK4 was selectively expressed in the primitive neuronal component of all GBM-PN cases while EGFR was positive in conventional GBM and glial component of GBM-PN, but was negative in the primitive neuronal component of all GBM-PN cases...
November 17, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/29150767/cell-migration-in-1d-and-2d-nanofiber-microenvironments
#3
Horacio M Estabridis, Aniket Jana, Amrinder Nain, David J Odde
Understanding how cells migrate in fibrous environments is important in wound healing, immune function, and cancer progression. A key question is how fiber orientation and network geometry influence cell movement. Here we describe a quantitative, modeling-based approach toward identifying the mechanisms by which cells migrate in fibrous geometries having well controlled orientation. Specifically, U251 glioblastoma cells were seeded onto non-electrospinning Spinneret based tunable engineering parameters fiber substrates that consist of networks of suspended 400 nm diameter nanofibers...
November 17, 2017: Annals of Biomedical Engineering
https://www.readbyqxmd.com/read/29149419/changes-in-chromatin-state-reveal-arnt2-at-a-node-of-a-tumorigenic-transcription-factor-signature-driving-glioblastoma-cell-aggressiveness
#4
Alexandra Bogeas, Ghislaine Morvan-Dubois, Elias A El-Habr, François-Xavier Lejeune, Matthieu Defrance, Ashwin Narayanan, Klaudia Kuranda, Fanny Burel-Vandenbos, Salwa Sayd, Virgile Delaunay, Luiz G Dubois, Hugues Parrinello, Stéphanie Rialle, Sylvie Fabrega, Ahmed Idbaih, Jacques Haiech, Ivan Bièche, Thierry Virolle, Michele Goodhardt, Hervé Chneiweiss, Marie-Pierre Junier
Although a growing body of evidence indicates that phenotypic plasticity exhibited by glioblastoma cells plays a central role in tumor development and post-therapy recurrence, the master drivers of their aggressiveness remain elusive. Here we mapped the changes in active (H3K4me3) and repressive (H3K27me3) histone modifications accompanying the repression of glioblastoma stem-like cells tumorigenicity. Genes with changing histone marks delineated a network of transcription factors related to cancerous behavior, stem state, and neural development, highlighting a previously unsuspected association between repression of ARNT2 and loss of cell tumorigenicity...
November 17, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/29149169/the-role-of-allee-effect-in-modelling-post-resection-recurrence-of-glioblastoma
#5
Zoltan Neufeld, William von Witt, Dora Lakatos, Jiaming Wang, Balazs Hegedus, Andras Czirok
Resection of the bulk of a tumour often cannot eliminate all cancer cells, due to their infiltration into the surrounding healthy tissue. This may lead to recurrence of the tumour at a later time. We use a reaction-diffusion equation based model of tumour growth to investigate how the invasion front is delayed by resection, and how this depends on the density and behaviour of the remaining cancer cells. We show that the delay time is highly sensitive to qualitative details of the proliferation dynamics of the cancer cell population...
November 17, 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/29149079/sphingosine-1-phosphate-s1p-signaling-in-glioblastoma-multiforme-a-systematic-review
#6
REVIEW
Shailaja Mahajan-Thakur, Sandra Bien-Möller, Sascha Marx, Henry Schroeder, Bernhard H Rauch
The multifunctional sphingosine-1-phosphate (S1P) is a lipid signaling molecule and central regulator in the development of several cancer types. In recent years, intriguing information has become available regarding the role of S1P in the progression of Glioblastoma multiforme (GBM), the most aggressive and common brain tumor in adults. S1P modulates numerous cellular processes in GBM, such as oncogenesis, proliferation and survival, invasion, migration, metastasis and stem cell behavior. These processes are regulated via a family of five G-protein-coupled S1P receptors (S1PR1-5) and may involve mainly unknown intracellular targets...
November 17, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29148898/enhancement-of-invadopodia-activity-in-glioma-cells-by-sublethal-doses-of-irradiation-and-temozolomide
#7
Leon Mao, Clarissa A Whitehead, Lucia Paradiso, Andrew H Kaye, Andrew P Morokoff, Rodney B Luwor, Stanley S Stylli
OBJECTIVE Glioblastoma is the most common primary central nervous system tumor in adults. These tumors are highly invasive and infiltrative and result in tumor recurrence as well as an extremely poor patient prognosis. The current standard of care involves surgery, radiotherapy, and chemotherapy. However, previous studies have suggested that glioblastoma cells that survive treatment are potentially more invasive. The goal of this study was to investigate whether this increased phenotype in surviving cells is facilitated by actin-rich, membrane-based structures known as invadopodia...
November 17, 2017: Journal of Neurosurgery
https://www.readbyqxmd.com/read/29147863/prognostic-relevance-of-programmed-cell-death-ligand-1-expression-in-glioblastoma
#8
Kyu Sang Lee, Kyoungyul Lee, Sumi Yun, Seyoung Moon, Yujun Park, Jung Ho Han, Chae-Yong Kim, Hye Seung Lee, Gheeyoung Choe
The aim of this study was to determine the clinicopathological significance of programmed cell death ligand 1 (PD-L1) expression in glioblastoma (GBM). In a retrospective cohort of 115 consecutive patients with GBM, PD-L1 expression was determined using immunohistochemistry (IHC). Membranous and fibrillary PD-L1 staining of any intensity in > 5% neoplastic cells and tumour infiltrating immune cells (TIIs) was considered positive staining. In addition, isocitrate dehydrogenase-1 (IDH-1) (R132H) expression and cluster of differentiation 3 (CD3)-positive T-cell infiltration were investigated using IHC...
November 16, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/29147815/atp-binding-cassette-transporters-limit-the-brain-penetration-of-wee1-inhibitors
#9
Mark C de Gooijer, Levi C M Buil, Jos H Beijnen, Olaf van Tellingen
Introduction Wee1 is an important kinase involved in the G2 cell cycle checkpoint and frequently upregulated in intracranial neoplasms such as glioblastoma (GBM) and diffuse intrinsic pontine glioma (DIPG). Two small molecules are available that target Wee1, AZD1775 and PD0166285, and clinical trials with AZD1775 have already been started. Since GBM and DIPG are highly invasive brain tumors, they are at least to some extent protected by the blood-brain barrier (BBB) and its ATP-binding cassette (ABC) efflux transporters...
November 17, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/29147652/identification-of-potent-chloride-intracellular-channel-protein-1-inhibitors-from-traditional-chinese-medicine-through-structure-based-virtual-screening-and-molecular-dynamics-analysis
#10
Wei Wang, Minghui Wan, Dongjiang Liao, Guilin Peng, Xin Xu, Weiqiang Yin, Guixin Guo, Funeng Jiang, Weide Zhong, Jianxing He
Chloride intracellular channel 1 (CLIC1) is involved in the development of most aggressive human tumors, including gastric, colon, lung, liver, and glioblastoma cancers. It has become an attractive new therapeutic target for several types of cancer. In this work, we aim to identify natural products as potent CLIC1 inhibitors from Traditional Chinese Medicine (TCM) database using structure-based virtual screening and molecular dynamics (MD) simulation. First, structure-based docking was employed to screen the refined TCM database and the top 500 TCM compounds were obtained and reranked by X-Score...
2017: BioMed Research International
https://www.readbyqxmd.com/read/29147637/subtotal-resection-of-a-thalamic-glioblastoma-multiforme-through-transsylvian-approach
#11
Rouzbeh Motiei-Langroudi, Homa Sadeghian, Alireza M Mohammadi
Glioblastoma multiforme (GBM) is a malignant brain tumor with an ominous prognosis. The standard treatment includes maximal safe resection plus adjuvant therapy. Thalamic GBMs, however, are unfavorable for microsurgical removal because of deep location and proximity to critical structures. We present a patient presenting with progressive hemiparesis and decreased consciousness with a large thalamic GBM who underwent subtotal resection through a transsylvian approach. His clinical and neurologic condition improved after surgery and he survived nine months after surgery...
September 7, 2017: Curēus
https://www.readbyqxmd.com/read/29147621/in-depth-immunophenotyping-of-patients-with-glioblastoma-multiforme-impact-of-steroid-treatment
#12
Guranda Chitadze, Charlotte Flüh, Elgar Susanne Quabius, Sandra Freitag-Wolf, Christian Peters, Marcus Lettau, Jaydeep Bhat, Daniela Wesch, Hans-Heinrich Oberg, Stefanie Luecke, Ottmar Janssen, Michael Synowitz, Janka Held-Feindt, Dieter Kabelitz
Despite aggressive treatment regimens based on surgery and radiochemotherapy, the prognosis of patients with grade IV glioblastoma multiforme (GBM) remains extremely poor, calling for alternative options such as immunotherapy. Immunological mechanisms including the Natural Killer Group 2 member D (NKG2D) receptor-ligand system play an important role in tumor immune surveillance and targeting the NKG2D system might be beneficial. However, before considering any kind of immunotherapy, a precise characterization of the immune system is important, particularly in GBM patients where conventional therapies with impact on the immune system are frequently co-administered...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/29147435/gliosarcoma-in-young-adults-a-rare-variant-of-glioblastoma
#13
Neha Kakkar, Jaspreet Kaur, Gunjesh Kumar Singh, Pragya Singh, Fouzia Siraj, Ajay Gupta
Gliosarcoma is a rare central nervous system (CNS) malignancy. It is characterized by classical biphasic histological pattern with both glial and sarcomatous components, often seen in fifth and sixth decade of life. They are generally located in the supratentorial region. Due to its rarity, exact treatment recommendations are not available in literature. Since it is considered as a variant of glioblastoma multiforme (GBM), it is treated with surgery followed by adjuvant radiotherapy and temozolomide-based chemotherapy...
April 2017: World Journal of Oncology
https://www.readbyqxmd.com/read/29146721/development-of-a-function-blocking-antibody-against-fibulin-3-as-targeted-reagent-for-glioblastoma
#14
Mohan Sobhana Nandhu, Prajna Behera, Vivek Bhaskaran, Sharon L Longo, Lina M Barrera-Arenas, Sadhak Sengupta, Diego J Rodriguez-Gil, E Antonio Chiocca, Mariano S Viapiano
PURPOSE: We sought a novel approach against glioblastomas (GBM) focused on targeting signaling molecules localized in the tumor extracellular matrix (ECM). We investigated fibulin-3, a glycoprotein that forms the ECM scaffold of GBMs and promotes tumor progression by driving Notch and NF-kB signaling. EXPERIMENTAL DESIGN: We used deletion constructs to identify a key signaling motif of fibulin-3. A monoclonal antibody (mAb428.2) was generated against this epitope and extensively validated for specific detection of human fibulin-3...
November 16, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29146145/adars-and-editing-the-role-of-a-to-i-rna-modification-in-cancer-progression
#15
REVIEW
Kajsa Fritzell, Lidi Xu, Jens Lagergren, Marie Öhman
Cancer arises when pathways that control cell functions such as proliferation and migration are dysregulated to such an extent that cells start to divide uncontrollably and eventually spread throughout the body, ultimately endangering the survival of an affected individual. It is well established that somatic mutations are important in cancer initiation and progression as well as in creation of tumor diversity. Now also modifications of the transcriptome are emerging as a significant force during the transition from normal cell to malignant tumor...
November 13, 2017: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/29145888/tgf-%C3%AE-2-initiates-autophagy-via-smad-and-non-smad-pathway-to-promote-glioma-cells-invasion
#16
Chao Zhang, Xin Zhang, Ran Xu, Bin Huang, An-Jing Chen, Chao Li, Jian Wang, Xin-Gang Li
BACKGROUND: Glioblastoma multiforme (GBM) is characterized by lethal aggressiveness and patients with GBM are in urgent need for new therapeutic avenues to improve quality of life. Current studies on tumor invasion focused on roles of cytokines in tumor microenvironment and numerous evidence suggests that TGF-β2 is abundant in glioma microenvironment and vital for glioma invasion. Autopagy is also emerging as a critical factor in aggressive behaviors of cancer cells; however, the relationship between TGF-β2 and autophagy in glioma has been poorly understood...
November 16, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/29144730/cancer-protrusions-on-a-tightrope-nanofiber-curvature-contrast-quantitates-single-protrusion-dynamics
#17
Brian Koons, Puja Sharma, Zhou Ye, Apratim Mukherjee, Meng Horng Lee, Denis Wirtz, Bahareh Behkam, Amrinder Singh Nain
Cell migration is studied with the traditional focus on protrusion driven cell body displacement, while less is known on morphodynamics of individual protrusions themselves, especially in fibrous environments mimicking extracellular matrix. Here, using suspended fibers, we report integrative and multiscale abilities to study protrusive behavior independent of cell body migration. By manipulating the diameter of fibers in orthogonal directions, we constrain cell migration along large diameter (2 µm) base fibers, while solely allowing cells to sense, initiate, and mature protrusions on orthogonally deposited high curvature-low diameter (~100, 200 and 600 nm) protrusive fibers and low-curvature (~300 and 600 nm width) protrusive flat ribbons...
November 16, 2017: ACS Nano
https://www.readbyqxmd.com/read/29143922/pre-treatment-lymphopenia-and-indication-of-tumor-induced-systemic-immunosuppression-in-medulloblastoma
#18
Seema Patel, Shiyang Wang, Matija Snuderl, Matthias A Karajannis
The presence of tumor-induced systemic immune suppression, including lymphopenia, has been recognized in adult patients with glioblastoma for several decades, and pre-treatment neutrophil-to-lymphocyte count ratio (NLCR) is associated with inferior clinical outcome in patients with glioblastoma. Whether tumor-induced systemic immune suppression is also present in children with malignant brain tumors is not known. We performed a retrospective analysis of pretreatment neutrophil and lymphocyte counts in pediatric patients with medulloblastoma (MB) compared to a control group of children with posterior fossa pilocytic astrocytoma (PA)...
November 16, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/29143921/dichloroacetate-induced-intracellular-acidification-in-glioblastoma-in-vivo-detection-using-aacid-cest-mri-at-9-4%C3%A2-tesla
#19
Mohammed Albatany, Alex Li, Susan Meakin, Robert Bartha
Intracellular pH (pHi) plays an important role in the maintenance of normal cell function, and is maintained within a narrow range by the activity of transporters located at the plasma membrane. Modulation of tumor pHi may influence proliferation, apoptosis, chemotherapy resistance, and thermosensitivity. Chemical exchange saturation transfer (CEST) is a novel MRI contrast mechanism that is dependent on cellular pH. Amine and amide concentration-independent detection (AACID) is a recently developed CEST contrast method that is intracellular pH (pHi) weighted...
November 16, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/29142297/5-aminolevulinic-acid-guided-sampling-of-glioblastoma-microenvironments-identifies-pro-survival-signaling-at-infiltrative-margins
#20
James L Ross, Lee A D Cooper, Jun Kong, David Gutman, Merete Williams, Carol Tucker-Burden, Myles R McCrary, Alexandros Bouras, Milota Kaluzova, William D Dunn, Duc Duong, Constantinos G Hadjipanayis, Daniel J Brat
Glioblastoma (GBM) contains diverse microenvironments with uneven distributions of oncogenic alterations and signaling networks. The diffusely infiltrative properties of GBM result in residual tumor at neurosurgical resection margins, representing the source of relapse in nearly all cases and suggesting that therapeutic efforts should be focused there. To identify signaling networks and potential druggable targets across tumor microenvironments (TMEs), we utilized 5-ALA fluorescence-guided neurosurgical resection and sampling, followed by proteomic analysis of specific TMEs...
November 15, 2017: Scientific Reports
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