35,967 results match your criteria Glioblastoma Multiforme


Tumor targeting peptides: novel therapeutic strategies in glioblastoma.

Authors:
Drazen Raucher

Curr Opin Pharmacol 2019 Feb 15;47:14-19. Epub 2019 Feb 15.

Department of Cell and Molecular Biology, University of Mississippi Medical Center, Jackson, MS, United States. Electronic address:

Peptides are a promising new therapeutic approach for glioblastoma with potential for more effective targeting and fewer devastating side effects compared to conventional cancer therapies. With the specificity to target receptors which are uniquely or overexpressed on cancer cells as well as accurately targeting dysregulated signaling pathways, peptides demonstrate a high potential for the treatment of even the most aggressive cancers. By binding to these targets, peptides can be used to deliver drugs, serve as antagonists to various ligands, or, given some inherent anticancer activity, provide additional treatment options alone or in combination therapy. Read More

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http://dx.doi.org/10.1016/j.coph.2019.01.006DOI Listing
February 2019

WIN55,212-2 induces caspase-independent apoptosis on human glioblastoma cells by regulating HSP70, p53 and Cathepsin D.

Toxicol In Vitro 2019 Feb 15. Epub 2019 Feb 15.

Experimental Pathology Laboratory, Federal University of São João del Rei (UFSJ), 400, Sebastião Gonçalves Coelho, Chanadour, Divinópolis, MG, Brazil. Electronic address:

Despite the standard approaches to treat the highly aggressive and invasive glioblastoma (GBM), it remains incurable. In this sense, cannabinoids highlight as a promising tool, because this tumor overexpresses CB1 and/or CB2 receptors and being, therefore, can be susceptible to cannabinoids treatment. Thus, this work investigated the action of the cannabinoid agonist WIN55-212-2 on GBM cell lines and non-malignant cell lines, in vitro and in vivo. Read More

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http://dx.doi.org/10.1016/j.tiv.2019.02.009DOI Listing
February 2019

Octa-arginine boosts the penetration of elastin-like polypeptide nanoparticles in 3D cancer models.

Eur J Pharm Biopharm 2019 Feb 15. Epub 2019 Feb 15.

Department of Biochemistry, Radboud Institute for Molecular Life Sciences (RIMLS), Radboud University Medical Center, PO Box 9101, 6500 HB Nijmegen, The Netherlands. Electronic address:

Elastin-like polypeptide (ELP) nanoparticles are a versatile platform for targeted drug delivery. As for any type of nanocarrier system an important challenge remains the ability of deep (tumor) tissue penetration. In this study, ELP particles with controlled surface density of the cell-penetrating peptide (CPP) octa-arginine (R8) were created by temperature-induced co-assembly. Read More

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http://dx.doi.org/10.1016/j.ejpb.2019.02.010DOI Listing
February 2019

Measles Virus-Based Treatments Trigger a Pro-inflammatory Cascade and a Distinctive Immunopeptidome in Glioblastoma.

Mol Ther Oncolytics 2019 Mar 31;12:147-161. Epub 2018 Dec 31.

Interdisciplinary Division of Neuro-Oncology, Hertie Institute for Clinical Brain Research, Departments of Neurology and Neurosurgery, University Hospital Tübingen, Eberhard Karls University Tübingen, Tübingen 72076, Germany.

Glioblastoma is an aggressive primary brain tumor with bad prognosis. On the other hand, oncolytic measles virus (MeV) therapy is an experimental glioma treatment strategy with clinical safety and first evidence of anti-tumoral efficacy. Therefore, we investigated the combination of MeV with conventional therapies by cytotoxic survival assays in long-term glioma cell lines LN229, LNZ308, and glioma stem-like GS8 cells, as well as the basal viral infectivity in primary glioblastoma cultures T81/16, T1094/17, and T708/16. Read More

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http://dx.doi.org/10.1016/j.omto.2018.12.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6365369PMC

Targeting JUN, CEBPB, and HDAC3: A Novel Strategy to Overcome Drug Resistance in Hypoxic Glioblastoma.

Front Oncol 2019 1;9:33. Epub 2019 Feb 1.

Department of Oncology, Xinqiao Hospital, Army Medical University, Chongqing, China.

Hypoxia is a predominant feature in glioblastoma (GBM) and contributes greatly to its drug resistance. However, the molecular mechanisms which are responsible for the development of the resistant phenotype of GBM under hypoxic conditions remain unclear. To analyze the key pathways promoting therapy resistance in hypoxic GBM, we utilized the U87-MG cell line as a human GBM cell model and the human brain HEB cell line as a non-neoplastic brain cell model. Read More

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http://dx.doi.org/10.3389/fonc.2019.00033DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6367651PMC
February 2019

Novel window for cancer nanotheranostics: non-invasive ocular assessments of tumor growth and nanotherapeutic treatment efficacy .

Biomed Opt Express 2019 Jan 11;10(1):151-166. Epub 2018 Dec 11.

EyePod Small Animal Ocular Imaging Laboratory, University of California, Davis, CA 95616, USA.

In cancer research there is a fundamental need for animal models that allow the longitudinal visualization and quantification of tumor development, nanotherapeutic delivery, the tumor microenvironment including blood vessels, macrophages, fibroblasts, immune cells, and extracellular matrix, and the tissue response to treatment. To address this need, we developed a novel mouse ocular xenograft model. Green fluorescent protein (GFP) expressing human glioblastoma cells (between 500 and 10,000) were implanted into the subretinal space of immunodeficient mice (56 eyes). Read More

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http://dx.doi.org/10.1364/BOE.10.000151DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6363190PMC
January 2019

The pro-apoptotic Bcl-2 family member Harakiri (HRK) induces cell death in glioblastoma multiforme.

Cell Death Discov 2019 8;5:64. Epub 2019 Feb 8.

1Brain Cancer Research and Therapy Laboratory, Koç University School of Medicine, Istanbul, Turkey.

Harakiri (HRK) is a BH3-only protein of the Bcl-2 family and regulates apoptosis by interfering with anti-apoptotic Bcl-2 and Bcl-xL proteins. While its function is mainly characterized in the nervous system, its role in tumors is ill-defined with few studies demonstrating HRK silencing in tumors. In this study, we investigated the role of HRK in the most aggressive primary brain tumor, glioblastoma multiforme (GBM). Read More

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http://dx.doi.org/10.1038/s41420-019-0144-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6368544PMC
February 2019

Clinico-Histomorphological and Immunohistochemical Profile of Anaplastic Pleomorphic Xanthoastrocytoma: Report of Five Cases and Review of Literature.

Int J Hematol Oncol Stem Cell Res 2018 Oct;12(4):265-272

Department of Neurosurgery, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India.

Pleomorphic xanthoastrocytoma is a rare tumour of children and young adults, particularly for those with features of anaplasia. This retrospective study comprises five cases of anaplastic pleomorphic xanthoastrocytomas diagnosed over a period of 4 years in a tertiary care institute. A detailed clinicopathological and immunohistochemical profile of the tumours were noted from the hospital database. Read More

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October 2018

Preoperative MRI-radiomics features improve prediction of survival in glioblastoma patients over MGMT methylation status alone.

Oncotarget 2019 Jan 18;10(6):660-672. Epub 2019 Jan 18.

Department of Medical Physics, Memorial Sloan Kettering Cancer Center, New York, New York, USA.

Background: Glioblastoma (GBM) is the most common malignant central nervous system tumor, and promoter hypermethylation in this tumor has been shown to be associated with better prognosis. We evaluated the capacity of radiomics features to add complementary information to status, to improve the ability to predict prognosis.

Methods: 159 patients with untreated GBM were included in this study and divided into training and independent test sets. Read More

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http://dx.doi.org/10.18632/oncotarget.26578DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6363013PMC
January 2019

A case of crossed cerebellar diaschisis on follow-up positron emission tomography/computed tomography with (F) fluoro-D-glucose after treatment for glioblastoma.

World J Nucl Med 2019 Jan-Mar;18(1):71-73

Department of Nuclear Medicine and Positron Emission Tomography/Computed Tomography, General Hospital of Athens "Evangelismos," Athens, Greece.

Crossed cerebellar diaschisis (CCD) represents the reduction of blood flow, metabolism, and oxygen consumption in the cerebellar hemisphere contralateral to a cerebral focal lesion. This phenomenon is the result of remote metabolic effects of cerebral lesions and it has been described since the first attempts for functional imaging of the brain, almost 40 years ago. Nevertheless, its clinical significance remains uncertain and new ways to use imaging of CCD for prognosis or assessment of novel therapies are being investigated. Read More

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http://dx.doi.org/10.4103/wjnm.WJNM_15_18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6357717PMC

Engineered MSC/Nanomedicine Spheroid as an Active Drug Delivery Platform for Combinational Glioblastoma Therapy.

Nano Lett 2019 Feb 18. Epub 2019 Feb 18.

Mesenchymal stem cell (MSC) has been increasingly applied to cancer therapy because of its tumor-tropic capability. However, short retention at target tissue and limited payload option hinder the progress of MSC-based cancer therapy. Herein, we proposed a hybrid spheroid/nanomedicine system, comprising MSC spheroid entrapping drug-loaded nanocomposite to address these limitations. Read More

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http://dx.doi.org/10.1021/acs.nanolett.8b04697DOI Listing
February 2019

Nucleolipids of the Nucleoside Antibiotics Formycin A and B: Synthesis and Biomedical Characterization particularly using Glioblastoma Cells.

Chem Biodivers 2019 Feb 18. Epub 2019 Feb 18.

Institute for Anatomy and Cell Biology, Department of Medical Cell Biology, Philipps-University Marburg, Robert-Koch-Str. 8, D-35032 Marburg, GERMANY.

Two lipophilic derivatives of formycin A (1) and formycin B (5) carrying an O-2',3'-ethyllevulinate ketal group have been prepared. These were base-alkylated at N(1) (for 1) and N(1) and N(6) (for 5) with both, isopentenyl or all-trans farnesyl residues. Upon the prenylation side reactions were observed, resulting in the formation of nucleolipids with a novel tricyclic nucleobase (→ 4a,b). Read More

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http://dx.doi.org/10.1002/cbdv.201900012DOI Listing
February 2019

Cancer genetic markers according to radiotherapeutic response in patients with primary glioblastoma - Radiogenomic approach for precision medicine.

Radiother Oncol 2019 Feb 31;131:66-74. Epub 2018 Dec 31.

Institute for Refractory Cancer Research, Research Institute for Future Medicine, Samsung Medical Center, Seoul, Republic of Korea; Department of Health Sciences and Technology, Samsung Advanced Institute for Health Science & Technology, Sungkyunkwan University, Seoul, Republic of Korea; Department of Neurosurgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.

Background And Purpose: To find genetic markers associated with response to radiotherapy (RT) in glioblastoma (GB) patients.

Materials And Methods: From Jan 2009 to Dec 2016, 161 patients with newly diagnosed IDH-wild type GB were treated with surgery and adjuvant concurrent chemoradiotherapy with the Stupp's regimen, and then genomic research proceeded with their surgical specimens. Among the 161 patients, 49 with clinically measurable disease on postoperative MRI were analyzed. Read More

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http://dx.doi.org/10.1016/j.radonc.2018.11.025DOI Listing
February 2019

Improved survival of glioblastoma patients treated at academic and high-volume facilities: a hospital-based study from the National Cancer Database.

J Neurosurg 2019 Feb 15:1-12. Epub 2019 Feb 15.

1The Vivian L. Smith Department of Neurosurgery, The University of Texas Health Science Center at Houston McGovern Medical School.

OBJECTIVEThe present study was designed to explore the association between facility type (academic center [AC] vs non-AC), facility volume (high-volume facility [HVF] vs low-volume facility [LVF]), and outcomes of glioblastoma (GBM) treatment.METHODSBased on the National Cancer Database (NCDB), GBM patients were categorized by treatment facility type (non-AC vs AC) and volume [4 categories (G1-G4): < 5.0, 5. Read More

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http://dx.doi.org/10.3171/2018.10.JNS182247DOI Listing
February 2019

A multicenter phase II study of temozolomide plus disulfiram and copper for recurrent temozolomide-resistant glioblastoma.

J Neurooncol 2019 Feb 15. Epub 2019 Feb 15.

Washington University School of Medicine, St. Louis, MO, USA.

Purpose: Preclinical studies have suggested promising activity for the combination of disulfiram and copper (DSF/Cu) against glioblastoma (GBM) including re-sensitization to temozolomide (TMZ). A previous phase I study demonstrated the safety of combining DSF/Cu with adjuvant TMZ for newly diagnosed GBM. This phase II study aimed to estimate the potential effectiveness of DSF/Cu to re-sensitize recurrent GBM to TMZ. Read More

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http://dx.doi.org/10.1007/s11060-019-03125-yDOI Listing
February 2019

Mammalian Target of Rapamycin 2 (MTOR2) and C-MYC Modulate Glucosamine-6-Phosphate Synthesis in Glioblastoma (GBM) Cells Through Glutamine: Fructose-6-Phosphate Aminotransferase 1 (GFAT1).

Cell Mol Neurobiol 2019 Feb 15. Epub 2019 Feb 15.

Center of Reproduction, development and aging, Institute of Translational Medicine, Cancer Centre, Faculty of Health Sciences, University of Macau, Hengqin, 999078, Macau, SAR, China.

Glucose and glutamine are two essential ingredients for cell growth. Glycolysis and glutaminolysis can be linked by glutamine: fructose-6-phosphate aminotransferase (GFAT, composed of GFAT1 and GFAT2) that catalyzes the synthesis of glucosamine-6-phosphate and glutamate by using fructose-6-phosphate and glutamine as substrates. The role of mammalian target of rapamycin (MTOR, composed of MTOR1 and MTOR2) in regulating glycolysis has been explored in human cancer cells. Read More

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http://dx.doi.org/10.1007/s10571-019-00659-7DOI Listing
February 2019

Letter: Thalamic Glioblastoma: Clinical Presentation, Management Strategies, and Outcomes.

Neurosurgery 2019 Feb 16. Epub 2019 Feb 16.

Department of Pediatric Xi'an Jiaotong University affiliated Children's Hospital, Xi'an Shaanxi, China.

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http://dx.doi.org/10.1093/neuros/nyz009DOI Listing
February 2019

Discrimination Between Solitary Brain Metastasis and Glioblastoma Multiforme by Using ADC-Based Texture Analysis: A Comparison of Two Different ROI Placements.

Acad Radiol 2019 Feb 12. Epub 2019 Feb 12.

Department of Radiology, Guangzhou First People's Hospital, Guangzhou Medical University, 1 Panfu Road, Guangzhou, Guangdong 510108, China; Department of Radiology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong, China. Electronic address:

Rationale And Objectives: To explore the value of texture analysis based on the apparent diffusion coefficient (ADC) value and the effect of region of interest (ROI) placements in distinguishing glioblastoma multiforme (GBM) from solitary brain metastasis (sMET).

Materials And Methods: Sixty-two patients with pathologically confirmed GBM (n = 36) and sMET (n = 26) were retrospectively included. All patients underwent diffusion-weighted imaging with b values of 0 and 1000 s/mm, and the ADC maps were generated automatically. Read More

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http://dx.doi.org/10.1016/j.acra.2019.01.010DOI Listing
February 2019
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Anti-Invasion and Antiangiogenic Effects of Stellettin B through Inhibition of the Akt/Girdin Signaling Pathway and VEGF in Glioblastoma Cells.

Cancers (Basel) 2019 Feb 14;11(2). Epub 2019 Feb 14.

Department of Neurosurgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, No. 123, Dapi Road, Niaosong District, Kaohsiung City 833, Taiwan.

Angiogenesis and invasion are highly related with tumor metastatic potential and recurrence prediction in the most aggressive brain cancer, glioblastoma multiforme (GBM). For the first time, this study reveals that marine-sponge-derived stellettin B reduces angiogenesis and invasion. We discovered that stellettin B reduces migration of glioblastoma cells by scratch wound healing assay and invasion via chamber transwell assay. Read More

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http://dx.doi.org/10.3390/cancers11020220DOI Listing
February 2019

Histologic findings associated with laser interstitial thermotherapy for glioblastoma multiforme.

Diagn Pathol 2019 Feb 15;14(1):19. Epub 2019 Feb 15.

Department of Neurological Surgery, The Ohio State University Wexner Medical Center, 410 West 10th Avenue, Doan 1047, Columbus, OH, 43210, USA.

Background: Laser-interstitial thermal therapy (LITT) has been supported by some authors as an ablative treatment of glioblastoma multiforme (GBM). Although the effects of LITT have been modeled in vivo, the histologic effects in a clinical circumstance have not been described. We analyzed tissue from a patient who underwent LITT as primary treatment for GBM. Read More

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http://dx.doi.org/10.1186/s13000-019-0794-4DOI Listing
February 2019

How far will the Voyager take us?

Authors:
Victor A Levin

CNS Oncol 2019 Feb 15:CNS26. Epub 2019 Feb 15.

Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77005, USA.

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http://dx.doi.org/10.2217/cns-2018-0019DOI Listing
February 2019

Effects of solvent used for fabrication on drug loading and release kinetics of electrosprayed temozolomide-loaded PLGA microparticles for the treatment of glioblastoma.

J Biomed Mater Res B Appl Biomater 2019 Feb 15. Epub 2019 Feb 15.

Department of Health and Biomedical Sciences, University of Texas Rio Grande Valley, One West University Blvd., Brownsville, Texas, 78520.

Glioblastoma multiforme (GBM) is the most common and invasive form of malignant brain tumors and despite advances in surgery, radiotherapy, and chemotherapy, the survival of patients with GBM still remains poor. Temozolomide (TMZ) is the chemotherapy drug that is most commonly given orally after surgical resection of these tumors. In this study, the effects of solvents (i. Read More

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http://dx.doi.org/10.1002/jbm.b.34324DOI Listing
February 2019
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Phenotypic Transformation of Astrocytes Into Tumor-Supportive Cells: Glioblastoma Cell Vesicle Release.

Neurosurgery 2019 Mar;84(3):E144-E145

Brain Tumor Center Department of Neurosurgery Lenox Hill Hospital Donald and Barbara Zucker School of Medicine at Hofstra Northwell New York, New York.

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http://dx.doi.org/10.1093/neuros/nyy624DOI Listing

G2/M inhibitors as pharmacotherapeutic opportunities for glioblastoma: the old, the new, and the future.

Cancer Biol Med 2018 Nov;15(4):354-374

Department of Pediatrics.

Glioblastoma (GBM) is one of the deadliest tumors and has a median survival of 3 months if left untreated. Despite advances in rationally targeted pharmacological approaches, the clinical care of GBM remains palliative in intent. Since the majority of altered signaling cascades involved in cancer establishment and progression eventually affect cell cycle progression, an alternative approach for cancer therapy is to develop innovative compounds that block the activity of crucial molecules needed by tumor cells to complete cell division. Read More

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http://dx.doi.org/10.20892/j.issn.2095-3941.2018.0030DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6372908PMC
November 2018

Triple-drug Therapy With Bevacizumab, Irinotecan, and Temozolomide Plus Tumor Treating Fields for Recurrent Glioblastoma: A Retrospective Study.

Front Neurol 2019 31;10:42. Epub 2019 Jan 31.

The Vivian L. Smith Department of Neurosurgery, The University of Texas Health Science Center at Houston (UTHealth), McGovern Medical School, Houston, TX, United States.

Clinical studies treating pediatric and adult solid tumors, such as glioblastoma (GBM), with a triple-drug regimen of temozolomide (TMZ), bevacizumab (BEV), and irinotecan (IRI) [TBI] have demonstrated various efficacies, but with no unexpected toxicities. The TBI regimen has never been studied in recurrent GBM (rGBM) patients. In this retrospective study, we investigated the outcomes and side effects of rGBM patients who had received the TBI regimen. Read More

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http://dx.doi.org/10.3389/fneur.2019.00042DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6366009PMC
January 2019

Corrigendum: HAX-1 Protects Glioblastoma Cells From Apoptosis Through the Akt1 Pathway.

Front Cell Neurosci 2019 31;13:13. Epub 2019 Jan 31.

Department of Neuro-interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

[This corrects the article DOI: 10.3389/fncel.2017. Read More

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http://dx.doi.org/10.3389/fncel.2019.00013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6366153PMC
January 2019

Intravital imaging of glioma border morphology reveals distinctive cellular dynamics and contribution to tumor cell invasion.

Sci Rep 2019 Feb 14;9(1):2054. Epub 2019 Feb 14.

Hubrecht Institute-KNAW & University Medical Center Utrecht, Uppsalalaan 8, 3584 CT, Utrecht, The Netherlands.

The pathogenesis of glioblastoma (GBM) is characterized by highly invasive behavior allowing dissemination and progression. A conclusive image of the invasive process is not available. The aim of this work was to study invasion dynamics in GBM using an innovative in vivo imaging approach. Read More

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http://dx.doi.org/10.1038/s41598-019-38625-4DOI Listing
February 2019

Targeting cholesterol metabolism in glioblastoma: a new therapeutic approach in cancer therapy.

J Investig Med 2019 Feb 14. Epub 2019 Feb 14.

Department of Human Anatomy and Cell Sciences, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada.

Glioblastoma multiforme (GBM) is the most aggressive malignant brain tumor known with a poor survival rate despite current advances in the field of cancer. Additional research into the pathophysiology of GBM is urgently needed given the devastating nature of this disease. Recent studies have revealed the unique cellular physiology of GBM cells as compared with healthy astrocytes. Read More

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http://dx.doi.org/10.1136/jim-2018-000962DOI Listing
February 2019

Atypical anaplastic astrocytoma with unique molecular features and diffuse leptomeningeal spread in a child with long-term survival.

BMJ Case Rep 2019 Feb 13;12(2). Epub 2019 Feb 13.

Neurosciences and Pediatrics, University of California San Diego, San Diego, California, USA.

Paediatric high-grade gliomas, including glioblastoma and anaplastic astrocytoma, make up 8%-12% of paediatric central nervous system tumours and have poor prognosis, with 2-year survival less than 30% and overall survival less than 10%. The only known prognostic factors in this population include extent of resection and tumour histological grade. We present the case of a 9-year-old boy with disseminated anaplastic astrocytoma treated with subtotal resection, craniospinal radiation and temozolomide, with 8-year survival despite metastatic disease at presentation and subtotal resection. Read More

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http://dx.doi.org/10.1136/bcr-2018-228153DOI Listing
February 2019

Chemistry and biology of ophiobolin A and its congeners.

Bioorg Med Chem Lett 2019 Feb 7. Epub 2019 Feb 7.

Department of Chemistry and Biochemistry, Texas State University, San Marcos, TX 78666, USA; Department of Chemistry, North Caucasus Federal University, 1a Pushkin St, Stavropol 355009, Russian Federation.

Ophiobolin A is a fungal secondary metabolite that was found to have significant activity against apoptosis-resistant glioblastoma cells through the induction of a non-apoptotic cell death, offering an innovative strategy to combat this aggressive cancer. The current article aims to make the bridge between the anti-cancer effects of ophiobolin A and its unique reaction with primary amines and suggests that pyrrolylation of lysine residues on its intracellular target protein(s) and/or phosphatidylethanolamine lipid is responsible for its biological effects. The article also discusses chemical derivatization of ophiobolin A to establish first synthetically generated structure-activity relationship. Read More

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http://dx.doi.org/10.1016/j.bmcl.2019.02.007DOI Listing
February 2019

Comprehensive gene expression meta-analysis identifies signature genes that distinguish microglia from peripheral monocytes/macrophages in health and glioma.

Acta Neuropathol Commun 2019 Feb 14;7(1):20. Epub 2019 Feb 14.

Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany.

Monocytes/macrophages have begun to emerge as key cellular modulators of brain homeostasis and central nervous system (CNS) disease. In the healthy brain, resident microglia are the predominant macrophage cell population; however, under conditions of blood-brain barrier leakage, peripheral monocytes/macrophages can infiltrate the brain and participate in CNS disease pathogenesis. Distinguishing these two populations is often challenging, owing to a paucity of universally accepted and reliable markers. Read More

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http://dx.doi.org/10.1186/s40478-019-0665-yDOI Listing
February 2019

Targeted design and identification of AC1NOD4Q to block activity of HOTAIR by abrogating the scaffold interaction with EZH2.

Clin Epigenetics 2019 Feb 14;11(1):29. Epub 2019 Feb 14.

Department of Neurosurgery, Tianjin Medical University General Hospital, Lab of Neuro-oncology, Tianjin Neurological Institute, Key Laboratory of Post-Neuro injury Neuro-repair and Regeneration in Central Nervous System, Ministry of Education and Tianjin City, Tianjin, 300052, China.

Background: Nearly 25% of long intergenic non-coding RNAs (lincRNAs) recruit chromatin-modifying proteins (e.g., EZH2) to silence target genes. Read More

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http://dx.doi.org/10.1186/s13148-019-0624-2DOI Listing
February 2019

Effective Immunotherapy of Glioblastoma in an Adolescent with Constitutional Mismatch Repair-Deficiency Syndrome.

Klin Onkol 2019 ;32(1):70-74

Background: Individuals with constitutional mismatch repair-deficiency syndrome (CMMR-D) are characterised by early occurrence of colon cancer, haematological malignancies, and brain tumors (malignant gliomas, high-grade gliomas) in childhood, adolescence, and early adulthood. High mutational tumor burden is typical of glioblastoma in CMMR-D patients and could be a reason why this type of glioblastoma responds well to immunotherapies, including those that employ checkpoint inhibitors.

Observation: We describe a case of an adolescent with CMMR-D that had been genetically proven by whole exome sequencing (c. Read More

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http://dx.doi.org/10.14735/amko201970DOI Listing
January 2019
1 Read

Virus-Based Immunotherapy of Glioblastoma.

Cancers (Basel) 2019 Feb 5;11(2). Epub 2019 Feb 5.

Department of Immunology, Genetics, and Pathology, Science for Life Laboratory, Uppsala University, 75185 Uppsala, Sweden.

Glioblastoma (GBM) is the most common type of primary brain tumor in adults. Despite recent advances in cancer therapy, including the breakthrough of immunotherapy, the prognosis of GBM patients remains dismal. One of the new promising ways to therapeutically tackle the immunosuppressive GBM microenvironment is the use of engineered viruses that kill tumor cells via direct oncolysis and via stimulation of antitumor immune responses. Read More

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http://dx.doi.org/10.3390/cancers11020186DOI Listing
February 2019

Constitutive activation of Notch2 signalling confers chemoresistance to neural stem cells via transactivation of fibroblast growth factor receptor-1.

Stem Cell Res 2019 Feb 7;35:101390. Epub 2019 Feb 7.

Department of Biomedicine, Pharmazentrum, University of Basel, 4056 Basel, Switzerland. Electronic address:

Notch signalling regulates neural stem cell (NSC) proliferation, differentiation and survival for the correct development and functioning of the central nervous system. Overactive Notch2 signalling has been associated with poor prognosis of aggressive brain tumours, such as glioblastoma multiforme (GBM). We recently reported that constitutive expression of the Notch2 intracellular domain (N2ICD) enhances proliferation and gliogenesis in NSCs. Read More

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http://dx.doi.org/10.1016/j.scr.2019.101390DOI Listing
February 2019

A Novel MKL Method for GBM Prognosis Prediction by Integrating Histopathological Image and Multi-omics Data.

IEEE J Biomed Health Inform 2019 Feb 11. Epub 2019 Feb 11.

Glioblastoma Multiforme (GBM) is one of the most malignant brain tumors with very short prognosis expectation. To improve patients' clinical treatment and their life quality after surgery. Researches have developed tremendous in silico models and tools for predicting GBM prognosis based on molecular datasets and have earned great success. Read More

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http://dx.doi.org/10.1109/JBHI.2019.2898471DOI Listing
February 2019

Small-molecule inhibition of prostaglandin E receptor 2 impairs cyclooxygenase-associated malignant glioma growth.

Br J Pharmacol 2019 Feb 14. Epub 2019 Feb 14.

Division of Pharmaceutical Sciences, James L. Winkle College of Pharmacy, University of Cincinnati, Cincinnati, Ohio, USA.

Background And Purpose: Induced cyclooxygenase-2 (COX-2) in malignant gliomas causes excessive synthesis of prostaglandin E2 (PGE ) that is thought to facilitate the brain tumor growth and invasion. However, which downstream PGE receptor subtype (i.e. Read More

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http://doi.wiley.com/10.1111/bph.14622
Publisher Site
http://dx.doi.org/10.1111/bph.14622DOI Listing
February 2019
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The Path Toward PET-Guided Radiation Therapy for Glioblastoma in Laboratory Animals: A Mini Review.

Front Med (Lausanne) 2019 29;6. Epub 2019 Jan 29.

Department of Radiology and Nuclear Medicine, Ghent University, Ghent, Belgium.

Glioblastoma is the most aggressive and malignant primary brain tumor in adults. Despite the current state-of-the-art treatment, which consists of maximal surgical resection followed by radiation therapy, concomitant, and adjuvant chemotherapy, progression remains rapid due to aggressive tumor characteristics. Several new therapeutic targets have been investigated using chemotherapeutics and targeted molecular drugs, however, the intrinsic resistance to induced cell death of brain cells impede the effectiveness of systemic therapies. Read More

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http://dx.doi.org/10.3389/fmed.2019.00005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6361864PMC
January 2019

Induction of MET Receptor Tyrosine Kinase Down-regulation through Antibody-mediated Receptor Clustering.

Sci Rep 2019 Feb 13;9(1):1988. Epub 2019 Feb 13.

Department of Chemistry and Biochemistry, University of Nevada, Las Vegas, Las Vegas, NV, 89154-4003, USA.

The proto-oncoprotein MET is a receptor tyrosine kinase that plays a key role in cancer cell growth and invasion. We have used fluorescence-tagged antibodies to activate MET in live serum-starved glioblastoma cells and monitor the fate of antibody-bound MET receptor in single cell-based assays. We found that the antibodies induced rapid and transient formation of highly polarized MET clusters on the plasma membrane and promoted the activation of MET, resembling the initial effects of binding to its ligand, HGF. Read More

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http://dx.doi.org/10.1038/s41598-018-36963-3DOI Listing
February 2019

The US11 gene of Herpes Simplex Virus 1 promotes neuroinvasion and periocular replication following corneal infection.

J Virol 2019 Feb 13. Epub 2019 Feb 13.

Department of Microbiology and Immunology, The Geisel School of Medicine at Dartmouth, Lebanon, NH.

Herpes simplex virus type 1 (HSV-1) cycles between phases of latency in sensory neurons and replication in mucosal sites. HSV-1 encodes two key proteins that antagonize the shutdown of host translation; US11 through preventing PKR activation, and ICP34.5 through mediating eIF2α dephosphorylation. Read More

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http://dx.doi.org/10.1128/JVI.02246-18DOI Listing
February 2019

Dynamic inosinome profiles reveal novel patient stratification and gender-specific differences in glioblastoma.

Genome Biol 2019 Feb 13;20(1):33. Epub 2019 Feb 13.

RNA Editing Lab., Oncohaematology Department, IRCCS Ospedale Pediatrico "Bambino Gesù", Viale San Paolo, 15 00146, Rome, Italy.

Background: Adenosine-to-inosine (A-to-I) RNA editing is an essential post-transcriptional mechanism mediated by ADAR enzymes that have been recently associated with cancer.

Results: Here, we characterize the inosinome signature in normal brain and de novo glioblastoma (GBM) using new metrics that re-stratify GBM patients according to their editing profiles and indicate this post-transcriptional event as a possible molecular mechanism for sexual dimorphism in GBM. We find that over 85% of de novo GBMs carry a deletion involving the genomic locus of ADAR3, which is specifically expressed in the brain. Read More

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https://genomebiology.biomedcentral.com/articles/10.1186/s13
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http://dx.doi.org/10.1186/s13059-019-1647-xDOI Listing
February 2019
4 Reads

Phenotypic Plasticity of Invasive Edge Glioma Stem-like Cells in Response to Ionizing Radiation.

Cell Rep 2019 Feb;26(7):1893-1905.e7

Department of Translational Molecular Pathology and Brain Tumor Center, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. Electronic address:

Unresectable glioblastoma (GBM) cells in the invading tumor edge can act as seeds for recurrence. The molecular and phenotypic properties of these cells remain elusive. Here, we report that the invading edge and tumor core have two distinct types of glioma stem-like cells (GSCs) that resemble proneural (PN) and mesenchymal (MES) subtypes, respectively. Read More

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http://dx.doi.org/10.1016/j.celrep.2019.01.076DOI Listing
February 2019
1 Read
7.207 Impact Factor

Design, Synthesis, and Biological Evaluation of Novel Allosteric Protein Disulfide Isomerase Inhibitors.

J Med Chem 2019 Feb 13. Epub 2019 Feb 13.

Protein disulfide isomerase (PDI) is responsible for nascent protein folding in the endoplasmic reticulum (ER) and is critical for glioblastoma survival. To improve the potency of lead PDI inhibitor BAP2 ((E)-3-(3-(4-hydroxyphenyl)-3-oxoprop-1-en-1-yl)benzonitrile), we designed and synthesized 67 novel analogues. We determined that PDI inhibition relied on the A ring hydroxyl group of the chalcone scaffold and cLogP increase in the sulfonamide chain improved potency. Read More

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http://dx.doi.org/10.1021/acs.jmedchem.8b01951DOI Listing
February 2019

Quantifying Uncertainty and Robustness in a Biomathematical Model-Based Patient-Specific Response Metric for Glioblastoma.

JCO Clin Cancer Inform 2019 Feb(3):1-8

1 Mayo Clinic Arizona, Phoenix, AZ.

Purpose: Glioblastomas, lethal primary brain tumors, are known for their heterogeneity and invasiveness. A growing body of literature has been developed demonstrating the clinical relevance of a biomathematical model, the proliferation-invasion model, of glioblastoma growth. Of interest here is the development of a treatment response metric, days gained (DG). Read More

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http://dx.doi.org/10.1200/CCI.18.00066DOI Listing
February 2019

Glioblastoma Recurrence and the Role of O-Methylguanine-DNA Methyltransferase Promoter Methylation.

JCO Clin Cancer Inform 2019 Feb(3):1-12

1 University of Minnesota Twin Cities, Minneapolis, MN.

Tumor recurrence in glioblastoma multiforme (GBM) is often attributed to acquired resistance to the standard chemotherapeutic agent, temozolomide (TMZ). Promoter methylation of the DNA repair gene MGMT (O-methylguanine-DNA methyltransferase) has been associated with sensitivity to TMZ, whereas increased expression of MGMT has been associated with TMZ resistance. Clinical studies have observed a downward shift in MGMT methylation percentage from primary to recurrent stage tumors; however, the evolutionary processes that drive this shift and more generally the emergence and growth of TMZ-resistant tumor subpopulations are still poorly understood. Read More

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http://dx.doi.org/10.1200/CCI.18.00062DOI Listing
February 2019

Atypical Presentation of Glioblastoma Multiforme.

Eur J Case Rep Intern Med 2018 27;5(9):000954. Epub 2018 Sep 27.

Neurology Department, Henry Ford Health System, Detroit, MI, USA.

Background: Glioblastoma multiforme (GBM) is a highly malignant glial tumour classified by the World Health Organization (WHO) as a stage IV astrocytoma. It varies in shape and size and can be cystic, vascular and necrotic. It often appears as a ring-enhancing lesion on magnetic resonance imaging (MRI). Read More

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http://dx.doi.org/10.12890/2018_000954DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6346815PMC
September 2018

Eradication of glioblastoma by immuno-virotherapy with a retargeted oncolytic HSV in a preclinical model.

Oncogene 2019 Feb 12. Epub 2019 Feb 12.

Department of Experimental Medicine, University of Genoa, Genoa, Italy.

Oncolytic herpes simplex viruses are proving to be effective in clinical trials against a number of cancers. Here, R-115, an oncolytic herpes simplex virus retargeted to human erbB-2, fully virulent in its target cells, and armed with murine interleukin-12 was evaluated in a murine model of glioblastoma. We show that a single R-115 injection in established tumors resulted, in about 30% of animals, in the complete eradication of the tumor, otherwise invariably lethal. Read More

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http://dx.doi.org/10.1038/s41388-019-0737-2DOI Listing
February 2019

Ventricular-Subventricular Zone Contact by Glioblastoma is Not Associated with Molecular Signatures in Bulk Tumor Data.

Sci Rep 2019 Feb 12;9(1):1842. Epub 2019 Feb 12.

Department of Neurological Surgery, Vanderbilt University Medical Center, Nashville, TN, USA.

Whether patients with glioblastoma that contacts the ventricular-subventricular zone stem cell niche (VSVZ + GBM) have a distinct survival profile from VSVZ - GBM patients independent of other known predictors or molecular profiles is unclear. Using multivariate Cox analysis to adjust survival for widely-accepted predictors, hazard ratios (HRs) for overall (OS) and progression free (PFS) survival between VSVZ + GBM and VSVZ - GBM patients were calculated in 170 single-institution patients and 254 patients included in both The Cancer Genome (TCGA) and Imaging (TCIA) atlases. An adjusted, multivariable analysis revealed that VSVZ contact was independently associated with decreased survival in both datasets. Read More

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http://dx.doi.org/10.1038/s41598-018-37734-wDOI Listing
February 2019

A simple three-dimensional hydrogel platform enables ex vivo cell culture of patient and PDX tumors for assaying their response to clinically relevant therapies.

Mol Cancer Ther 2019 Feb 12. Epub 2019 Feb 12.

Department of Neurosurgery, Cedars-Sinai Medical Center

A cell culture platform that enables ex vivo tissue growth from patients or patient-derived xenograft (PDX) models and assesses sensitivity to approved therapies (e.g. Temozolomide, TMZ) in a clinically relevant timeframe would be very useful in translational research and personalized medicine. Read More

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http://dx.doi.org/10.1158/1535-7163.MCT-18-0359DOI Listing
February 2019