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targeted therapy for glioblastoma multiforme

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https://www.readbyqxmd.com/read/29651429/therapeutic-potential-of-thymoquinone-in-glioblastoma-treatment-targeting-major-gliomagenesis-signaling-pathways
#1
REVIEW
Fabliha Ahmed Chowdhury, Md Kamal Hossain, A G M Mostofa, Maruf Mohammad Akbor, Muhammad Shahdaat Bin Sayeed
Glioblastoma multiforme (GBM) is one of the most devastating brain tumors with median survival of one year and presents unique challenges to therapy because of its aggressive behavior. Current treatment strategy involves surgery, radiotherapy, immunotherapy, and adjuvant chemotherapy even though optimal management requires a multidisciplinary approach and knowledge of potential complications from both the disease and its treatment. Thymoquinone (TQ), the main bioactive component of Nigella sativa L., has exhibited anticancer effects in numerous preclinical studies...
2018: BioMed Research International
https://www.readbyqxmd.com/read/29651419/management-of-glioblastoma-multiforme-in-a-patient-treated-with-ketogenic-metabolic-therapy-and-modified-standard-of-care-a-24-month-follow-up
#2
Ahmed M A Elsakka, Mohamed Abdel Bary, Eman Abdelzaher, Mostafa Elnaggar, Miriam Kalamian, Purna Mukherjee, Thomas N Seyfried
Few advances have been made in overall survival for glioblastoma multiforme (GBM) in more than 40 years. Here, we report the case of a 38-year-old man who presented with chronic headache, nausea, and vomiting accompanied by left partial motor seizures and upper left limb weakness. Enhanced brain magnetic resonance imaging revealed a solid cystic lesion in the right partial space suggesting GBM. Serum testing revealed vitamin D deficiency and elevated levels of insulin and triglycerides. Prior to subtotal tumor resection and standard of care (SOC), the patient conducted a 72-h water-only fast...
2018: Frontiers in Nutrition
https://www.readbyqxmd.com/read/29615902/drug-repositioning-in-glioblastoma-a-pathway-perspective
#3
REVIEW
Sze Kiat Tan, Anna Jermakowicz, Adnan K Mookhtiar, Charles B Nemeroff, Stephan C Schürer, Nagi G Ayad
Glioblastoma multiforme (GBM) is the most malignant primary adult brain tumor. The current standard of care is surgical resection, radiation, and chemotherapy treatment, which extends life in most cases. Unfortunately, tumor recurrence is nearly universal and patients with recurrent glioblastoma typically survive <1 year. Therefore, new therapies and therapeutic combinations need to be developed that can be quickly approved for use in patients. However, in order to gain approval, therapies need to be safe as well as effective...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29614978/a-35-gene-signature-discriminates-between-rapidly-and-slowly-progressing-glioblastoma-multiforme-and-predicts-survival-in-known-subtypes-of-the-cancer
#4
Azeez A Fatai, Junaid Gamieldien
BACKGROUND: Gene expression can be employed for the discovery of prognostic gene or multigene signatures cancer. In this study, we assessed the prognostic value of a 35-gene expression signature selected by pathway and machine learning based methods in adjuvant therapy-linked glioblastoma multiforme (GBM) patients from the Cancer Genome Atlas. METHODS: Genes with high expression variance was subjected to pathway enrichment analysis and those having roles in chemoradioresistance pathways were used in expression-based feature selection...
April 3, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29611298/in-vitro-evaluation-of-225-ac-dota-substance-p-for-targeted-alpha-therapy-of-glioblastoma-multiforme
#5
Agnieszka Majkowska-Pilip, Maria Rius, Frank Bruchertseifer, Christos Apostolidis, Mirjam Weis, Milton Bonelli, Marta Laurenza, Leszek Królicki, Alfred Morgenstern
Glioblastoma multiforme (GBM) is the most malignant form of brain tumors with dismal prognosis despite treatment by surgery combined with radiotherapy and chemotherapy. The neuropeptide Substance P (SP) is the physiological ligand of the neurokinin-1 receptor (NK1-R), which is highly expressed in glioblastoma cells. Thus, SP represents a potential ligand for targeted alpha therapy. In this study, a protocol for the synthesis of SP labelled with the alpha emitter225 Ac was developed and binding affinity properties were determined...
April 2, 2018: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/29603594/serum-amyloid-a1-in-combination-with-integrin-%C3%AE-v%C3%AE-3-increases-glioblastoma-cells-mobility-and-progression
#6
Ching-Yu Lin, Shun-Tai Yang, Shing-Chuan Shen, Yi-Chen Hsieh, Fei-Ting Hsu, Cheng-Yu Chen, Yung-Hsiao Chiang, Jian-Ying Chuang, Kai-Yun Chen, Tsung-I Hsu, Wan-Chong Leong, Yu-Kai Su, Wei-Lun Lo, Yi-Shian Yeh, Yudha Nur Patria, Hsiu-Ming Shih, Che-Chang Chang, Szu-Yi Chou
Glioblastoma multiforme (GBM) is a highly malignant type of brain tumor found in humans. GBM cells reproduce quickly, and the median survival time for patients after therapy is approximately 1 year with a high relapse rate. Current therapies and diagnostic tools for GBM are limited; therefore, we searched for a more favorable therapeutic target or marker protein for both therapy and diagnosis. We used mass spectrometry (MS) analysis to identify GBM-associated marker proteins from human plasma and GBM cell cultures...
March 30, 2018: Molecular Oncology
https://www.readbyqxmd.com/read/29552147/silencing-ldha-inhibits-proliferation-induces-apoptosis-and-increases-chemosensitivity-to-temozolomide-in-glioma-cells
#7
Hui Di, Xinting Zhang, Yi Guo, Yanfang Shi, Chuan Fang, Yu Yuan, Jiwei Wang, Chao Shang, Wenzhe Guo, Chunhui Li
Glioblastoma multiforme (GBM) is a prevalent and aggressive disease, and the development of a novel therapy to better treat advanced GBM is urgently required. Lactate dehydrogenase A (LDHA), which functions as a key enzyme in transforming pyruvate into lactate, has attracted more attention in recent years due to its critical role in various types of advanced cancer. Previous data derived from the Oncomine database have shown that the expression of LDHA is higher in GBM tissues than that in corresponding normal control tissues...
April 2018: Oncology Letters
https://www.readbyqxmd.com/read/29549165/bivalent-chromatin-domains-in-glioblastoma-reveal-a-subtype-specific-signature-of-glioma-stem-cells
#8
Amelia Weber Hall, Anna M Battenhouse, Haridha Shivram, Adam R Morris, Matthew C Cowperthwaite, Max Shpak, Vishwanath R Iyer
Glioblastoma multiforme (GBM) can be clustered by gene expression into four main subtypes associated with prognosis and survival, but enhancers and other gene regulatory elements have not yet been identified in primary tumors. Here, we profiled six histone modifications and CTCF binding as well as gene expression in primary gliomas, and identified chromatin states that define distinct regulatory elements across the tumor genome. Enhancers in mesenchymal and classical tumor subtypes drove gene expression associated with cell migration and invasion, while enhancers in proneural tumors controlled genes associated with a less aggressive phenotype in GBM...
March 16, 2018: Cancer Research
https://www.readbyqxmd.com/read/29545552/the-mode-and-dynamics-of-glioblastoma-cell-invasion-into-a-decellularized-tissue-derived-extracellular-matrix-based-three-dimensional-tumor-model
#9
IlKyoo Koh, Junghwa Cha, Junseong Park, Junjeong Choi, Seok-Gu Kang, Pilnam Kim
Glioblastoma multiforme (GBM) is the most common brain tumor with very aggressive and infiltrative. Extracellular matrix (ECM) plays pivotal roles in the infiltrative characteristics of GBM. To understand the invasive characteristic of GBM, it is necessary to study cell-ECM interaction in the physiologically relevant biomimetic model that recapitulates the GBM-specific ECM microenvironment. Here, we propose biomimetic GBM-specific ECM microenvironment for studying mode and dynamics of glioblastoma cell invasion...
March 15, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29535786/association-of-glioblastoma-multiforme-stem-cell-characteristics-differentiation-and-microglia-marker-genes-with-patient-survival
#10
Sandra Bien-Möller, Ellen Balz, Susann Herzog, Laura Plantera, Silke Vogelgesang, Kerstin Weitmann, Carolin Seifert, Matthias A Fink, Sascha Marx, Angela Bialke, Chitra Venugopal, Sheila K Singh, Wolfgang Hoffmann, Bernhard H Rauch, Henry W S Schroeder
Patients with glioblastoma multiforme (GBM) are at high risk to develop a relapse despite multimodal therapy. Assumedly, glioma stem cells (GSCs) are responsible for treatment resistance of GBM. Identification of specific GSC markers may help to develop targeted therapies. Here, we performed expression analyses of stem cell (ABCG2, CD44, CD95, CD133, ELF4, Nanog, and Nestin) as well as differentiation and microglia markers (GFAP, Iba1, and Sparc) in GBM compared to nonmalignant brain. Furthermore, the role of these proteins for patient survival and their expression in LN18 stem-like neurospheres was analyzed...
2018: Stem Cells International
https://www.readbyqxmd.com/read/29527330/etv2-mediates-endothelial-transdifferentiation-of-glioblastoma
#11
Chengjian Zhao, Gustavo A Gomez, Yuwei Zhao, Yu Yang, Dan Cao, Jing Lu, Hanshuo Yang, Shuo Lin
Glioblastoma multiforme (GBM) is characterized by extensive endothelial hyperplasia. Recent studies suggest that a subpopulation of endothelial cells originates via vasculogenesis by the transdifferentiation of GBM tumor cells into endothelial cells (endo-transdifferentiation). The molecular mechanism underlying this process remains poorly defined. Here, we show that the expression of ETS variant 2 (ETV2), a master regulator of endothelial cell development, is highly correlated with malignancy. Functional studies demonstrate that ETV2 is sufficient and necessary for the transdifferentiation of a subpopulation of CD133+/Nestin+ GBM/neural stem cells to an endothelial lineage...
2018: Signal Transduction and Targeted Therapy
https://www.readbyqxmd.com/read/29525720/targeting-metabotropic-glutamate-receptors-in-the-treatment-of-primary-brain-tumors
#12
REVIEW
Luisa Iacovelli, Rosamaria Orlando, Alessandro Rossi, Paola Spinsanti, Daniela Melchiorri, Ferdinando Nicoletti
In spite of the recent advancement in the molecular characterization of malignant gliomas and medulloblastomas, the treatment of primary brain tumors remains suboptimal. The use of small molecule inhibitors of intracellular signaling pathways, inhibitors of angiogenesis, and immunotherapic agents is limited by systemic adverse effects, limited brain penetration, and, in some cases, lack of efficacy. Thus, adjuvant chemo-therapy and radiotherapy still remain the gold standard in the treatment of grade-IV astrocytoma (glioblastoma multiforme) and medulloblastoma...
March 8, 2018: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/29524050/role-of-chimeric-antigen-receptor-t-cell-therapy-in-glioblastoma-multiforme
#13
REVIEW
Vishal Jindal
Glioblastoma multiforme (GBM) is the most common primary malignant cancer of brain, which is extremely aggressive and carries a dreadful prognosis. Current treatment protocol runs around radiotherapy, surgical resection, and temozolomide with median overall survival of around 12-15 months. Due to its heterogeneity and mutational load, immunotherapy with chimeric antigen receptor (CAR) T cell therapy can be a promising treatment option for recurrent glioblastoma. Initial phase 1 studies have shown that this therapy is safe without dose-limiting side effects and it also has a better clinical outcome...
March 9, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29510196/pd-l1-confers-glioblastoma-multiforme-malignancy-via-ras-binding-and-ras-erk-emt-activation
#14
Xin Yao Qiu, Dian Xing Hu, Wen-Qiang Chen, Ruo Qiao Chen, Shi Rui Qian, Chun Yang Li, Yuan Jun Li, Xin Xin Xiong, Di Liu, Feng Pan, Shang Bin Yu, Xiao Qian Chen
Glioblastoma multiforme (GBM) is the most aggressive primary brain tumor due to the lack of effective therapeutic drugs. Cancer therapy targeting programmed cell death protein 1 (PD-1) or programmed death ligand-1 (PD-L1) is of revolutionary. However, the role of intrinsic PD-L1, which determines immune-therapy outcomes, remains largely unclear. Here we demonstrated an oncogenic role of PD-L1 via binding and activating Ras in GBM cells. RNA-sequencing transcriptome data revealed that PD-L1 significantly altered gene expression enriched in cell growth/migration/invasion pathways in human GBM cells...
March 3, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29507632/targeted-delivery-of-functionalized-upconversion-nanoparticles-for-externally-triggered-photothermal-photodynamic-therapies-of-brain-glioblastoma
#15
Yuan-Chung Tsai, Priya Vijayaraghavan, Wen-Hsuan Chiang, Hsin-Hung Chen, Te-I Liu, Ming-Yin Shen, Ayumu Omoto, Masao Kamimura, Kohei Soga, Hsin-Cheng Chiu
Therapeutic efficacy of glioblastoma multiforme (GBM) is often severely limited by poor penetration of therapeutics through blood-brain barrier (BBB) into brain tissues and lack of tumor targeting. In this regard, a functionalized upconversion nanoparticle (UCNP)-based delivery system which can target brain tumor and convert deep tissue-penetrating near-infrared (NIR) light into visible light for precise phototherapies on brain tumor was developed in this work. Methods : The UCNP-based phototherapy delivery system was acquired by assembly of oleic acid-coated UCNPs with angiopep-2/cholesterol-conjugated poly(ethylene glycol) and the hydrophobic photosensitizers...
2018: Theranostics
https://www.readbyqxmd.com/read/29499954/effects-of-aptamer-to-u87-egfrviii-cells-on-the-proliferation-radiosensitivity-and-radiotherapy-of-glioblastoma-cells
#16
Xingmei Zhang, Li Peng, Zhiman Liang, Zhewen Kou, Yue Chen, Guangwei Shi, Xiaowen Li, Yanling Liang, Fang Wang, Yusheng Shi
Glioblastoma multiforme (GBM) is the most prevalent and lethal malignant intracranial tumor in the brain, with very poor prognosis and survival. The epidermal growth factor receptor variant III (EGFRvIII) contributes to increased oncogenicity that does not occur through binding EGFR ligands and instead occurs through constitutive activation, which enhances glioma tumorigenicity and resistance to targeted therapy. Aptamers are nucleic acids with high affinity and specificity to targets selected by systematic evolution of ligands by exponential enrichment (SELEX), and are usually developed as antagonists of disease-associated factors...
March 2, 2018: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/29483208/characterization-of-abbv-221-a-tumor-selective-egfr-targeting-antibody-drug-conjugate
#17
Andrew C Phillips, Erwin R Boghaert, Kedar S Vaidya, Hugh D Falls, Michael J Mitten, Peter J DeVries, Lorenzo Benatuil, Chung-Ming Hsieh, Jonathan A Meulbroek, Sanjay C Panchal, Fritz G Buchanan, Kenneth R Durbin, Martin J Voorbach, David R Reuter, Sarah R Mudd, Lise I Loberg, Sherry L Ralston, Diana Cao, Hui K Gan, Andrew M Scott, Edward B Reilly
Depatuxizumab mafodotin (depatux-m, ABT-414) is a tumor-selective antibody drug conjugate (ADC) comprised of the anti-EGFR antibody ABT-806 and the monomethyl auristatin F (MMAF) warhead. Depatux-m has demonstrated promising clinical activity in glioblastoma multiforme (GBM) patients and is currently being evaluated in clinical trials in first-line and recurrent GBM disease settings. Depatux-m responses have been restricted to patients with amplified EGFR highlighting the need for therapies with activity against tumors with non-amplified EGFR overexpression...
February 26, 2018: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/29462960/the-role-of-wnt-signal-in-glioblastoma-development-and-progression-a-possible-new-pharmacological-target-for-the-therapy-of-this-tumor
#18
REVIEW
Mariachiara Zuccarini, Patricia Giuliani, Sihana Ziberi, Marzia Carluccio, Patrizia Di Iorio, Francesco Caciagli, Renata Ciccarelli
Wnt is a complex signaling pathway involved in the regulation of crucial biological functions such as development, proliferation, differentiation and migration of cells, mainly stem cells, which are virtually present in all embryonic and adult tissues. Conversely, dysregulation of Wnt signal is implicated in development/progression/invasiveness of different kinds of tumors, wherein a certain number of multipotent cells, namely "cancer stem cells", are characterized by high self-renewal and aggressiveness...
February 17, 2018: Genes
https://www.readbyqxmd.com/read/29458374/new-insights-into-long-noncoding-rnas-and-their-roles-in-glioma
#19
REVIEW
Zixuan Peng, Changhong Liu, Minghua Wu
Glioma is one of the most prevalent types of primary intracranial carcinoma with varying malignancy grades I-IV and histological subtypes, including astrocytomas, glioblastoma multiform (GBM), oligodendrogliomas and mixed tumors. Glioma is characterized by rapid cell proliferation and angiogenesis, and the WHO grade IV glioblastoma, which is highly malignant with poor prognosis because GBM stem-like cells (GSCs) are resistant to conventional therapy and easily recrudescent, accounts for the majority of gliomas...
February 19, 2018: Molecular Cancer
https://www.readbyqxmd.com/read/29457830/mirna-124-3p-neuropilin-1-nrp-1-axis-plays-an-important-role-in-mediating-glioblastoma-growth-and-angiogenesis
#20
Guilong Zhang, Lukui Chen, Ahsan Ali Khan, Bingqian Li, Bin Gu, Fan Lin, Xinhui Su, Jianghua Yan
Glioblastoma Multiforme (GBM) is the most lethal brain malignancy which involves multi-gene abnormality. Unfortunately, effective therapy against GBM is still lacking. Previously, we found that NRP-1 and its downstream NRP-1/GIPC1 pathway played an important role in GBM. In this study, we further investigated the upstream signaling of NRP-1 to understand how it is regulated. Firstly, we identified that hsa-miR-124-3p was miRNA differentially expressed in GBM and in normal brain tissues by high-throughput sequencing...
February 19, 2018: International Journal of Cancer. Journal International du Cancer
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