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Anti gbm

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https://www.readbyqxmd.com/read/28644886/complex-i-inhibition-augments-dichloroacetate-cytotoxicity-through-enhancing-oxidative-stress-in-vm-m3-glioblastoma-cells
#1
Nathan P Ward, Angela M Poff, Andrew P Koutnik, Dominic P D'Agostino
The robust glycolytic metabolism of glioblastoma multiforme (GBM) has proven them susceptible to increases in oxidative metabolism induced by the pyruvate mimetic dichloroacetate (DCA). Recent reports demonstrate that the anti-diabetic drug metformin enhances the damaging oxidative stress associated with DCA treatment in cancer cells. We sought to elucidate the role of metformin's reported activity as a mitochondrial complex I inhibitor in the enhancement of DCA cytotoxicity in VM-M3 GBM cells. Metformin potentiated DCA-induced superoxide production, which was required for enhanced cytotoxicity towards VM-M3 cells observed with the combination...
2017: PloS One
https://www.readbyqxmd.com/read/28634226/phostine-pst3-1a-targets-mgat5-and-inhibits-glioblastoma-initiating-cell-invasiveness-and-proliferation
#2
Zahra Hassani, Ali Saleh, Soumaya Turpault, Salim Khiati, Willy Morelle, Jacques Vignon, Jean-Philippe Hugnot, Emmanuelle Uro-Coste, Philippe Legrand, Marcel Delaforge, Séverine Loiseau, Ludovic Clarion, Marc Lecouvey, Jean-Noël Volle, David Virieux, Jean-Luc Pirat, Hugues Duffau, Norbert Bakalara
Glioblastoma multiforme (GBM) is the most common primary malignant brain tumor and accounts for a significant proportion of all primary brain tumors. Median survival after treatment is around 15 months. Remodeling of N-glycans by the N-acetylglucosamine glycosyltransferase (MGAT5) regulates tumoral development. Here, perturbation of MGAT5 enzymatic activity by the small-molecule inhibitor 3-Hydroxy-4,5-bis-benzyloxy-6-benzyloxymethyl-2-phenyl2-oxo-2λ5-[1,2]oxaphosphinane (PST3.1a) restrains GBM growth. In cell based assays it is demonstrated that PST3...
June 20, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28634045/egfr-egfrviii-remodels-the-cytoskeleton-via-epigenetic-silencing-of-ajap1-in-glioma-cells
#3
Chao Yang, Yan-Sheng Li, Qi-Xue Wang, Kai Huang, Jian-Wei Wei, Yun-Fei Wang, Jun-Hu Zhou, Kai-Kai Yi, Kai-Liang Zhang, Bing-Cong Zhou, Cong Liu, Liang Zeng, Chun-Sheng Kang
EGFR amplification and mutations are the most common oncogenic events in GBM. EGFR overexpression correlates with GBM invasion, but the underlying mechanisms are poorly understood. In a previous study, we showed that AJAP1 is involved in regulating F-actin to inhibit the invasive ability of GBM. In addition, in a GBM cell line, the AJAP1 promoter was highly bound by H3K27me3 and, through bioinformatics analysis, we found that AJAP1 expression was negatively correlated with EGFR. In this study, we found that the pathway downstream of EGFR had a higher activation level in GBM cell lines, which led to excessive tumor suppressor silencing...
June 19, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28627960/lack-of-functional-normalisation-of-tumour-vessels-following-anti-angiogenic-therapy-in-glioblastoma
#4
Nina Obad, Heidi Espedal, Radovan Jirik, Per Oystein Sakariassen, Cecilie Brekke Rygh, Morten Lund-Johansen, Torfinn Taxt, Simone P Niclou, Rolf Bjerkvig, Olivier Keunen
Neo-angiogenesis represents an important factor for the delivery of oxygen and nutrients to a growing tumour, and is considered to be one of the main pathodiagnostic features of glioblastomas (GBM). Anti-angiogenic therapy by vascular endothelial growth factor (VEGF) blocking agents has been shown to lead to morphological vascular normalisation resulting in a reduction of contrast enhancement as seen by magnetic resonance imaging (MRI). Yet the functional consequences of this normalisation and its potential for improved delivery of cytotoxic agents to the tumour are not known...
January 1, 2017: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/28621261/ag488-as-a-therapy-against-gliomas
#5
Jadith Ziegler, Anja Bastian, Megan Lerner, Lora Bailey-Downs, Debra Saunders, Nataliya Smith, Jake Sutton, James D Battiste, Michael A Ihnat, Aleem Gangjee, Rheal A Towner
High-grade gliomas such as glioblastomas (GBM) present a deadly prognosis following diagnosis and very few effective treatment options. Here, we investigate if the small molecule AG488 can be an effective therapy against GBM with both anti-angiogenic as well as an anti-microtubule inhibiting modalities, using a human G55 glioma xenograft model in nude mice. From in vitro studies, we report that AG488 incubation reduced cell viability in G55 and HMEC-1 cells more so than TMZ treatment, and AG488 treatment also decreased cell viability in normal astrocytes, but not as much as for G55 cells (p<0...
May 30, 2017: Oncotarget
https://www.readbyqxmd.com/read/28620891/population-pharmacokinetic-modeling-of-olaratumab-an-anti-pdgfr%C3%AE-human-monoclonal-antibody-in-patients-with-advanced-and-or-metastatic-cancer
#6
Gary Mo, John R Baldwin, Debra Luffer-Atlas, Robert L Ilaria, Ilaria Conti, Michael Heathman, Damien M Cronier
BACKGROUND AND OBJECTIVES: Olaratumab is a recombinant human monoclonal antibody that binds to platelet-derived growth factor receptor-α (PDGFRα). In a randomized phase II study, olaratumab plus doxorubicin met its predefined primary endpoint for progression-free survival and achieved a highly significant improvement in overall survival versus doxorubicin alone in patients with advanced or metastatic soft tissue sarcoma (STS). In this study, we characterize the pharmacokinetics (PKs) of olaratumab in a cancer patient population...
June 15, 2017: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/28619756/alpha-particle-enhanced-blood-brain-tumor-barrier-permeabilization-in-glioblastomas-using-integrin-alpha-v-beta-3-targeted-liposomes
#7
Anirudh Sattiraju, Xiaobing Xiong, Darpan N Pandya, Thaddeus J Wadas, Ang Xuan, Yao Sun, Youngkyoo Jung, Kiran Kumar Solingapuram Sai, Jay F Dorsey, King C Li, Akiva Mintz
<span style="font-size: 11.0pt; line-height: 200%; color: windowtext;">Glioblastoma (GBM) is the most common primary malignant astrocytoma characterized by extensive invasion, angiogenesis, hypoxia and micrometastasis. Despite the relatively leaky nature of GBM blood vessels, effective delivery of anti-tumor therapeutics has been a major challenge due to the complications caused by the blood brain barrier (BBB) and the highly torturous nature of newly formed tumor vasculature (blood tumor barrier-BTB)...
June 15, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28610419/gene-expression-profiling-of-chemokines-and-their-receptors-in-low-and-high-grade-astrocytoma
#8
Ira Sharma, Avninder Singh, Karam Chand Sharma, Sunita Saxena
Background: Despite intense interest in molecular characterization and searches for novel therapeutic targets, the glioblastoma remains a formidable clinical challenge. Among many contributors to gliomagenesis, chemokines have drawn special attention due to their involvement in a plethora of biological processes and pathological conditions. In the present study we aimed to elucidate any pro-gliomagenic chemokine axis and probable roles in development of glioblastoma multiforme (GBM). Method: An array of 84 chemokines, chemokine receptors and related genes were studied by real time PCR with comparison between low grade astrocytoma (diffuse astrocytoma – grade II) and high grade astrocytoma (glioblastoma multiforme – grade IV)...
May 1, 2017: Asian Pacific Journal of Cancer Prevention: APJCP
https://www.readbyqxmd.com/read/28604685/a-tnf-jnk-axl-erk-signaling-axis-mediates-primary-resistance-to-egfr-inhibition-in-glioblastoma
#9
Gao Guo, Ke Gong, Sonia Ali, Neha Ali, Shahzad Shallwani, Kimmo J Hatanpaa, Edward Pan, Bruce Mickey, Sandeep Burma, David H Wang, Santosh Kesari, Jann N Sarkaria, Dawen Zhao, Amyn A Habib
Aberrant epidermal growth factor receptor (EGFR) signaling is widespread in cancer, making the EGFR an important target for therapy. EGFR gene amplification and mutation are common in glioblastoma (GBM), but EGFR inhibition has not been effective in treating this tumor. Here we propose that primary resistance to EGFR inhibition in glioma cells results from a rapid compensatory response to EGFR inhibition that mediates cell survival. We show that in glioma cells expressing either EGFR wild type or the mutant EGFRvIII, EGFR inhibition triggers a rapid adaptive response driven by increased tumor necrosis factor (TNF) secretion, which leads to activation in turn of c-Jun N-terminal kinase (JNK), the Axl receptor tyrosine kinase and extracellular signal-regulated kinases (ERK)...
June 12, 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28602756/antrodia-cinnamomea-sensitizes-radio-chemo-therapy-of-cancer-stem-like-cells-by-modulating-microrna-expression
#10
Yu-Kai Su, Ping-Hsiao Shih, Wei-Hwa Lee, Oluwaseun Adebayo Bamodu, Alexander T H Wu, Chun-Chih Huang, Yew-Min Tzeng, Michael Hsiao, Chi-Tai Yeh, Chien-Min Lin
ETHNOPHARMACOLOGICAL RELEVANCE: The discovery of many tissue-specific cancer stem cells (CSCs) continues to attract scientific attention. These CSCs are considered to be associated with chemo- and radio-resistance, and consequently, failure of conventional anticancer therapies. The recent demonstration of several microRNAs as enhancers of tumorigenicity via modulation of epithelial-mesenchymal transition and cancer stemness, makes them putative novel therapeutic target in oncology. Antrodia cinnamomea is a Chinese traditional medicine with several biological functions including anti-inflammation, antioxidant, and cancer prevention...
June 8, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28597184/epithelial-membrane-protein-2-emp2-promotes-angiogenesis-in-glioblastoma-multiforme
#11
Yu Qin, Masamichi Takahashi, Kristopher Sheets, Horacio Soto, Jessica Tsui, Panayiotis Pelargos, Joseph P Antonios, Noriyuki Kasahara, Isaac Yang, Robert M Prins, Jonathan Braun, Lynn K Gordon, Madhuri Wadehra
Glioblastoma multiforme (GBM) is the most aggressive malignant brain tumor and is associated with an extremely poor clinical prognosis. One pathologic hallmark of GBM is excessive vascularization with abnormal blood vessels. Extensive investigation of anti-angiogenic therapy as a treatment for recurrent GBM has been performed. Bevacizumab, a monoclonal anti-vascular endothelial growth factor A (VEGF-A), suggests a progression-free survival benefit but no overall survival benefit. Developing novel anti-angiogenic therapies are urgently needed in controlling GBM growth...
June 9, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28593649/the-effect-of-gabapentin-and-tramadol-in-cancer-pain-induced-by-glioma-cell-in-rat-femur
#12
Janette Nallely Corona-Ramos, Myrna Déciga-Campos, Mario Romero-Piña, Luis A Medina, Issac Martínez-Racine, Osmar A Jaramillo-Morales, Patricia García-López, Francisco Javier López-Muñoz
Preclinical Research The presence of pain as part of the cancer process is variable. Glioblastoma multiform (GBM) can produce bone metastasis, a condition that involves other pathological phenotypes including neuropathic and inflammatory pain. Tramadol and gabapentin are drugs used in the treatment of neuropathic pain. However, there are no studies evaluating their analgesic effects in bone metastasis. We produced a pain model induced by the inoculation of glioma cells (10(5) ) into the rat femur, by perforating the intercodiloid fossa...
June 7, 2017: Drug Development Research
https://www.readbyqxmd.com/read/28591734/application-of-luteolin-nanomicelles-anti-glioma-effect-with-improvement-in-vitro-and-in-vivo
#13
Songping Zheng, Yongzhong Cheng, Yan Teng, Xiaoxiao Liu, Ting Yu, Yi Wang, Jiagang Liu, Yuzhu Hu, Cong Wu, Xiang Wang, Yanhui Liu, Chao You, Xiang Gao, Yuquan Wei
Glioblastoma multiforme (GBM) is one of the most common and malignant tumor. Luteolin, a polyphenolic compound, has been proposed to have anti-tumor activity against various cancers. However, the greatest obstacle in the administration of luteolin is its hydrophobicity as well as the low oral bioavailability. In this study, we formulated luteolin-loaded MPEG-PCL (Luteolin/MPEG-PCL) micelles aiming to improve its solubility in aqueous solution and investigate the anti-tumor effect on glioma in vitro and in vivo...
May 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/28590932/tdp-43-hdac6-axis-promoted-tumor-progression-and-regulated-nutrient-deprivation-induced-autophagy-in-glioblastoma
#14
Tzu-Wei Lin, Ming-Teh Chen, Liang-Tin Lin, Pin-I Huang, Wen-Liang Lo, Yi-Ping Yang, Kai-Hsi Lu, Yi-Wei Chen, Shih-Hwa Chiou, Cheng-Wen Wu
Glioblastoma Multiforme (GBM) is a lethal primary brain tumor with poor survival lifespan and dismal outcome. Surgical resection of GBM is greatly limited due to the biological significance of brain, giving rise to tumor relapse in GBM patients. Transactive response DNA binding protein-43 (TDP-43) is a DNA/RNA-binding protein known for causing neurodegenerative diseases through post-translational modification; but little is known about its involvement in cancer development. In this study, we found that nutrient deprivation in GBM cell lines elevated TDP-43 expression by a mechanism of evasion from ubiquitin-dependent proteolytic pathway, and subsequently activated the autophagy process...
May 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28590923/endoplasmic-reticulum-chaperone-prolyl-4-hydroxylase-beta-polypeptide-p4hb-promotes-malignant-phenotypes-in-glioma-via-mapk-signaling
#15
Stella Sun, Karrie M Y Kiang, Amy S W Ho, Derek Lee, Ming-Wai Poon, Fei-Fan Xu, Jenny K S Pu, Amanda N C Kan, Nikki P Y Lee, Xiao-Bing Liu, Kwan Man, Philip J R Day, Wai-Man Lui, Ching-Fai Fung, Gilberto K K Leung
Endoplasmic reticulum (ER) chaperone Prolyl 4-hydroxylase, beta polypeptide (P4HB) has previously been identified as a novel target for chemoresistance in glioblastoma multiforme (GBM). Yet its functional roles in glioma carcinogenesis remain elusive. In clinical analysis using human glioma specimens and Gene Expression Omnibus (GEO) profiles, we found that aberrant expression of P4HB was correlated with high-grade malignancy and an angiogenic phenotype in glioma. Furthermore, P4HB upregulation conferred malignant characteristics including proliferation, invasion, migration and angiogenesis in vitro, and increased tumor growth in vivo via the mitogen-activated protein kinase (MAPK) signaling pathway...
May 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/28583430/the-egfr-variant-iii-mutant-as-a-target-for-immunotherapy-of-glioblastoma-multiforme
#16
REVIEW
Dimitry A Chistiakov, Ivan V Chekhonin, Vladimir P Chekhonin
In epithelial tumors, the epidermal growth factor receptor (EGFR) controls key signaling pathways responsible for growth, proliferation, migration, and survival of tumor cells. The epidermal growth factor receptor variant III (EGFRvIII) is the most common EGFR mutation that occurs in up to 30% of high-grade gliomas especially glioblastoma multiforme (GBM). EGFRvIII arises from the deletion of exon 2-7 that leads to the formation of the constitutively activated mutant receptor incapable of binding any known ligand...
June 2, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28582760/current-status-and-future-therapeutic-perspectives-of-glioblastoma-multiforme-gbm-therapy-a-review
#17
REVIEW
Komal Anjum, Bibi Ibtesam Shagufta, Syed Qamar Abbas, Seema Patel, Ishrat Khan, Sayed Asmat Ali Shah, Najeeb Akhter, Syed Shams Ul Hassan
Glioblastoma multiforme (GBM) is the deadliest form of heterogeneous brain cancer. It affects an enormous number of patients every year and the survival is approximately 8 to 15 months. GBM has driven by complex signaling pathways and considered as a most challenging to treat. Standard treatment of GBM includes surgery, radiation therapy, chemotherapy and also the combined treatment. This review article described inter and intra- tumor heterogeneity of GMB. In addition, recent chemotherapeutic agents, with their mechanism of action have been defined...
June 2, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28573184/a-comparative-study-of-replication-incompetent-and-competent-adenoviral-therapy-mediated-immune-response-in-a-murine-glioma-model
#18
Julius W Kim, Jason Miska, Jacob S Young, Aida Rashidi, J Robert Kane, Wojciech K Panek, Deepak Kanojia, Yu Han, Irina V Balyasnikova, Maciej S Lesniak
Oncolytic virotherapy is a treatment approach with increasing clinical relevance, as indicated by the marked survival benefit seen in animal models and its current exploration in human patients with cancer. The use of an adenovirus vector for this therapeutic modality is common, has significant clinical benefit in animals, and its efficacy has recently been linked to an anti-tumor immune response that occurs following tumor antigen presentation. Here, we analyzed the adaptive immune system's response following viral infection by comparing replication-incompetent and replication-competent adenoviral vectors...
June 16, 2017: Molecular Therapy Oncolytics
https://www.readbyqxmd.com/read/28573137/rituximab-for-treatment-of-membranoproliferative-glomerulonephritis-and-c3-glomerulopathies
#19
REVIEW
Michael Rudnicki
Membranoproliferative glomerulonephritis (MPGN) is a histological pattern of injury resulting from predominantly subendothelial and mesangial deposition of immunoglobulins or complement factors with subsequent inflammation and proliferation particularly of the glomerular basement membrane. Recent classification of MPGN is based on pathogenesis dividing MPGN into immunoglobulin-associated MPGN and complement-mediated C3 glomerulonephritis (C3GN) and dense deposit disease (DDD). Current guidelines suggest treatment with steroids, cytotoxic agents with or without plasmapheresis only for subjects with progressive disease, that is, nephrotic range proteinuria and decline of renal function...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28571041/cbf1-is-clinically-prognostic-and-serves-as-a-target-to-block-cellular-invasion-and-chemoresistance-of-emt-like-glioblastoma-cells
#20
D Maciaczyk, D Picard, L Zhao, K Koch, D Herrera-Rios, G Li, V Marquardt, D Pauck, T Hoerbelt, W Zhang, D M Ouwens, M Remke, T Jiang, H J Steiger, J Maciaczyk, U D Kahlert
BACKGROUND: Glioblastoma is the most common and most lethal primary brain cancer. CBF1 (also known as Recombination signal Binding Protein for immunoglobulin kappa J, RBPJ) is the cardinal transcriptional regulator of the Notch signalling network and has been shown to promote cancer stem-like cells (CSCs) in glioblastoma. Recent studies suggest that some of the malignant properties of CSCs are mediated through the activation of pro-invasive programme of epithelial-to-mesenchymal transition (EMT)...
June 1, 2017: British Journal of Cancer
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