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https://www.readbyqxmd.com/read/29150788/ck4-ck6-cyclin-d1-p16-ink4a-and-egfr-expression-in-glioblastoma-with-a-primitive-neuronal-component
#1
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/29149079/sphingosine-1-phosphate-s1p-signaling-in-glioblastoma-multiforme-a-systematic-review
#2
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/29147863/prognostic-relevance-of-programmed-cell-death-ligand-1-expression-in-glioblastoma
#3
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
#4
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/29147637/subtotal-resection-of-a-thalamic-glioblastoma-multiforme-through-transsylvian-approach
#5
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
#6
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
#7
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
#8
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/29145888/tgf-%C3%AE-2-initiates-autophagy-via-smad-and-non-smad-pathway-to-promote-glioma-cells-invasion
#9
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/29143921/dichloroacetate-induced-intracellular-acidification-in-glioblastoma-in-vivo-detection-using-aacid-cest-mri-at-9-4%C3%A2-tesla
#10
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
#11
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
https://www.readbyqxmd.com/read/29138341/long-non-coding-rna-neat1-regulated-by-the-egfr-pathway-contributes-to-glioblastoma-progression-through-the-wnt-%C3%AE-catenin-pathway-by-scaffolding-ezh2
#12
Qun Chen, Jinquan Cai, Qixue Wang, Yunfei Wang, Mingyang Liu, Jingxuan Yang, Junhu Zhou, Chun-Sheng Kang, Min Li, Chuanlu Jiang
PURPOSE: Long noncoding RNAs have been implicated in gliomagenesis, but their mechanisms of action are mainly undocumented. Through public glioma mRNA expression datasets, we found that NEAT1 was a potential oncogene. We systematically analyzed the clinical significance and mechanism of NEAT1 in glioblastoma. EXPERIMENTAL DESIGN: Initially, we evaluated whether NEAT1 expression levels could be regulated by EGFR pathway activity. We subsequently evaluated the effect of NEAT1 on the WNT/β-Catenin pathway and its target binding gene...
November 14, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29136505/inhibition-of-trf1-telomere-protein-impairs-tumor-initiation-and-progression-in-glioblastoma-mouse-models-and-patient-derived-xenografts
#13
Leire Bejarano, Alberto J Schuhmacher, Marinela Méndez, Diego Megías, Carmen Blanco-Aparicio, Sonia Martínez, Joaquín Pastor, Massimo Squatrito, Maria A Blasco
Glioblastoma multiforme (GBM) is a deadly and common brain tumor. Poor prognosis is linked to high proliferation and cell heterogeneity, including glioma stem cells (GSCs). Telomere genes are frequently mutated. The telomere binding protein TRF1 is essential for telomere protection, and for adult and pluripotent stem cells. Here, we find TRF1 upregulation in mouse and human GBM. Brain-specific Trf1 genetic deletion in GBM mouse models inhibited GBM initiation and progression, increasing survival. Trf1 deletion increased telomeric DNA damage and reduced proliferation and stemness...
November 13, 2017: Cancer Cell
https://www.readbyqxmd.com/read/29136455/lbh589-inhibits-glioblastoma-growth-and-angiogenesis-through-suppression-of-hif-1%C3%AE-expression
#14
Zhi-Gang Yao, Wen-Huan Li, Fang Hua, Hong-Xia Cheng, Miao-Qing Zhao, Xi-Chao Sun, Ye-Jun Qin, Jia-Mei Li
Glioblastoma (GBM) is an angiogenic malignancy with a highly unfavorable prognosis. Angiogenesis in GBM represents an adaptation to a hypoxic microenvironment and is correlated with tumor growth, invasion, clinical recurrence, and lethality. LBH589 (also called panobinostat) is a histone deacetylase (HDAC) inhibitor with potent antitumor activity. In the current study, we investigated the mechanism and effects of LBH589 on GBM growth and hypoxia-induced angiogenesis in vitro and in vivo. To determine the antitumor and angiogenesis activity and mechanism of LBH589, we used cell proliferations in vitro and GBM xenografts in vivo...
December 1, 2017: Journal of Neuropathology and Experimental Neurology
https://www.readbyqxmd.com/read/29136334/identification-of-plasma-membrane-glycoproteins-specific-to-human-glioblastoma-multiforme-cells-using-lectin-arrays-and-lc-ms-ms
#15
YaeEun Park, Jeonghun Yeom, YoungSoo Kim, Hye Jin Lee, Ki-Cheol Han, SeungTaek Lee, Cheolju Lee, Ji Eun Lee
Glioblastoma, also known as glioblastoma multiforme (GBM), is the most malignant type of brain cancer and has poor prognosis with a median survival of less than one year. While the structural changes of tumor cell surface carbohydrates are known to be associated with invasive behavior of tumor cells, the cell surface glycoproteins to differentiate the low- and high-grade glioma cells can be potential diagnostic markers and therapeutic targets for GBMs. In the present study, lectin arrays consisting of eight lectins were employed to explore cell surface carbohydrate expression patterns on low-grade oligodendroglioma cells (Hs683) and GBM cells (T98G)...
November 14, 2017: Proteomics
https://www.readbyqxmd.com/read/29136244/a-molecular-cascade-modulates-map1b-and-confers-resistance-to-mtor-inhibition-in-human-glioblastoma
#16
Dan R Laks, Juan A Oses-Prieto, Alvaro G Alvarado, Jonathan Nakashima, Shreya Chand, Daniel B Azzam, Ankur A Gholkar, Jantzen Sperry, Kirsten Ludwig, Michael C Condro, Serli Nazarian, Anjelica Cardenas, Michelle Y S Shih, Robert Damoiseaux, Bryan France, Nicholas Orozco, Koppany Visnyei, Thomas J Crisman, Fuying Gao, Jorge Z Torres, Giovanni Coppola, Alma L Burlingame, Harley I Kornblum
Background: Clinical trials of therapies directed against nodes of the PI3K/AKT/mTOR signaling axis in Glioblastoma (GBM) have had disappointing results. Resistance to mTOR inhibitors limits their efficacy. Methods: To determine mechanisms of resistance to chronic mTOR inhibition, we performed tandem screens on patient-derived GBM cultures. Results: An unbiased phosphoproteomic screen quantified phosphorylation changes associated with chronic exposure to the mTOR inhibitor rapamycin and our analysis implicated a role for GSK3B attenuation in mediating resistance that was confirmed by functional studies...
November 9, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/29135607/targeting-the-perivascular-niche-in-brain-tumors
#17
Giorgio Seano
PURPOSE OF REVIEW: Brain tumors are composed of primary tumors of the central nervous system, such us glioblastoma (GBM), and secondary metastatic tumors, such as melanoma, non-Hodgkin lymphoma as well as lung and breast cancers. Brain tumors are highly deadly, and unfortunately not many improvements have been achieved to improve the survival of patients with brain tumors. Chemoradiation resistance is one of the most clinically relevant challenges faced in patients with brain tumors. The perivascular niche is one of the most relevant microenvironment hubs in brain tumors...
November 14, 2017: Current Opinion in Oncology
https://www.readbyqxmd.com/read/29135107/benefit-and-outcome-of-using-temozolomide-based-chemoradiotherapy-followed-by-temozolomide-alone-for-glioblastoma-in-clinical-practice
#18
Svetlana Salma, Igor Djan, Mladen Bjelan, Petar Vulekovic, Mico Novakovic, Vladimir Vidovic, Milos Lucic
PURPOSE: Temozolomide (TEM), an oral alkylating agent, has shown promising activity in the last 10 years in the treatment of glioblastoma multiforme (GBM). Our goal was to show the benefit of concomitant therapy involving 3D conformal radiotherapy and temozolomide in clinical practice. METHODS: This was a retrospective/prospective study and included a total of 113 patients with GBM diagnosis. Forty- seven patients received postoperative radiotherapy and 66 received concomitant temozolomide plus 3D conformal radiotherapy...
September 2017: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
https://www.readbyqxmd.com/read/29135106/evidence-for-the-efficacy-of-disulfiram-and-copper-combination-in-glioblastoma-multiforme-a-propos-of-a-case
#19
Petros N Karamanakos, Dimitrios T Trafalis, Dionysios J Papachristou, Eleftheria S Panteli, Maria Papavasilopoulou, Andreas Karatzas, Dimitrios Kardamakis, Georgios Nasioulas, Marios Marselos
Glioblastoma multiforme (GBM) is the most common and aggressive malignancy of the central nervous system. Treatment usually involves a combination of surgical resection, chemotherapy, and radiotherapy, but ultimately this condition is incurable. Besides the dismal prognosis of GBM, financial factors have also presented challenges for advancing treatments. Taking into consideration the high cost of developing new anticancer drugs as well as the fact that GBM is a rare disease, thus further limiting financial incentive for drug development, it becomes obvious that there has been growing interest for repurposing candidates...
September 2017: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
https://www.readbyqxmd.com/read/29133513/phase-ii-study-of-bevacizumab-and-vorinostat-for-patients-with-recurrent-world-health-organization-grade-4-malignant-glioma
#20
Ashley Ghiaseddin, David Reardon, Woody Massey, Alex Mannerino, Eric S Lipp, James E Herndon, Frances McSherry, Annick Desjardins, Dina Randazzo, Henry S Friedman, Katherine B Peters
LESSONS LEARNED: Combination regimen with bevacizumab (BEV) and vorinostat is well tolerated in patients with recurrent glioblastoma.Treatment of recurrent glioblastoma remains challenging as this study and others attempt to improve progression-free survival and overall survival with BEV-containing regimens. BACKGROUND: Recurrent glioblastoma (GBM; World Health Organization grade 4) continues to have a very poor prognosis. Bevacizumab (BEV) has been shown to improve progression-free survival (PFS) in recurrent GBM and is approved by the U...
November 13, 2017: Oncologist
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