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targeted therapy for glioblastoma multiforme

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https://www.readbyqxmd.com/read/29457830/mirna-124-3p-neuropilin-1-nrp-1-axis-plays-an-important-role-in-mediating-glioblastoma-growth-and-angiogenesis
#1
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
https://www.readbyqxmd.com/read/29453321/inhibition-of-cd95-cd95l-signaling-with-apg101-prevents-invasion-and-enhances-radiation-therapy-for-glioblastoma
#2
Jonas Blaes, Carina M Thomé, Philipp-Niclas Pfenning, Petra Rübmann, Felix Sahm, Antje Wick, Theresa Bunse, Torsten Schmenger, Jaromir Sykora, Andreas von Deimling, Benedikt Wiestler, Christian Merz, Manfred Jugold, Uwe Haberkorn, Amir Abdollahi, Jürgen Debus, Christian Gieffers, Claudia Kunz, Martin Bendszus, Michael Kluge, Michael Platten, Harald Fricke, Wolfgang Wick, Dieter Lemke
CD95 (Fas/APO-1), a death receptor family member, activity has been linked to tumorigenicity in multiple cancers, including glioblastoma multiforme (GBM). A phase II clinical trial on relapsed glioblastoma patients demonstrated that targeted inhibition of CD95 signaling via the CD95 ligand (CD95L) binding and neutralizing Fc-fusion protein APG101 (asunercept) prolonged patient survival. While CD95 signaling may be relevant for multiple aspects of tumor growth, the mechanism of action of APG101 in glioblastoma is not clear...
February 16, 2018: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29417946/micrornas-as-biomarkers-for-human-glioblastoma-progress-and-potential
#3
REVIEW
Shi-Wei Huang, Ni-da Ali, Lily Zhong, Jian Shi
Glioblastoma multiforme (GBM) is the most common malignant glioma. Despite innovative research efforts in tumor therapy, the outcome for most diagnosed patients remains poor; therefore, early diagnosis of GBM is the most effective method for achieving better patient outcomes. In recent years, combined research efforts including cellular, molecular, genetic, and bioinformatics methods have been used to investigate GBM, and the results show that variations in miRNA expression occur in GBM tissues and biological fluids...
February 8, 2018: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/29416606/sox9-pdk1-axis-is-essential-for-glioma-stem-cell-self-renewal-and-temozolomide-resistance
#4
Zhen Wang, Xiaoshan Xu, Nan Liu, Yingduan Cheng, Weilin Jin, Pengxing Zhang, Xin Wang, Hongwei Yang, Hui Liu, Yanyang Tu
Glioblastoma multiforme (GBM) is the most common and aggressive brain tumor with limited therapeutic options. Glioma stem cell (GSC) is thought to be greatly responsible for glioma tumor progression and drug resistance. But the molecular mechanisms of GSC deriving recurrence and drug resistance are still unclear. SOX9 (sex-determining region Y (SRY)-box9 protein), a transcription factor expressed in most solid tumors, is reported as a key regulator involved in maintaining cancer hallmarks including the GSCs state...
January 2, 2018: Oncotarget
https://www.readbyqxmd.com/read/29412012/application-of-an-assay-cascade-methodology-for-a-deep-preclinical-characterization-of-polymeric-nanoparticles-as-a-treatment-for-gliomas
#5
Cristina Fornaguera, Miguel Ángel Lázaro, Pau Brugada-Vilà, Irene Porcar, Ingrid Morera, Marta Guerra-Rebollo, Cristina Garrido, Núria Rubio, Jerónimo Blanco, Anna Cascante, Salvador Borrós
Glioblastoma multiforme (GBM) is the most devastating primary brain tumor due to its infiltrating and diffuse growth characteristics, a situation compounded by the lack of effective treatments. Currently, many efforts are being devoted to find novel formulations to treat this disease, specifically in the nanomedicine field. However, due to the lack of comprehensive characterization that leads to insufficient data on reproducibility, only a reduced number of nanomedicines have reached clinical phases. In this context, the aim of the present study was to use a cascade of assays that evaluate from physical-chemical and structural properties to biological characteristics, both in vitro and in vivo, and also to check the performance of nanoparticles for glioma therapy...
November 2018: Drug Delivery
https://www.readbyqxmd.com/read/29403545/bevacizumab-in-temozolomide-refractory-high-grade-gliomas-single-centre-experience-and-review-of-the-literature
#6
Jennifer Jeck, Rebecca Kassubek, Jan Coburger, Simone Edenhofer, Stefan S Schönsteiner, Albert C Ludolph, Bernd Schmitz, Jens Engelke, Regine Mayer-Steinacker, Jan Lewerenz, Lars Bullinger
Background: Despite multidisciplinary treatment approaches, the prognosis for patients with high-grade glioma (HGG) is poor, with a median overall survival (OS) of 14.6 months for glioblastoma multiforme (GB). As high levels of vascular endothelial growth factor A (VEGF) are found in HGG, targeted anti-antiangiogenic therapy using the humanized monoclonal antibody bevacizumab (BEV) was studied in a series of clinical trials. Still, the discrepancy of BEV's efficacy with regard to initial clinical and radiological response and its reported failure to prolong survival remains to be explained...
2018: Therapeutic Advances in Neurological Disorders
https://www.readbyqxmd.com/read/29396437/gene-therapy-for-human-glioblastoma-using-neurotropic-jc-virus-like-particles-as-a-gene-delivery-vector
#7
Chun-Nun Chao, Yu-Hsuan Yang, Mu-Sheng Wu, Ming-Chieh Chou, Chiung-Yao Fang, Mien-Chun Lin, Chien-Kuo Tai, Cheng-Huang Shen, Pei-Lain Chen, Deching Chang, Meilin Wang
Glioblastoma multiforme (GBM), the most common malignant brain tumor, has a short period of survival even with recent multimodality treatment. The neurotropic JC polyomavirus (JCPyV) infects glial cells and oligodendrocytes and causes fatal progressive multifocal leukoencephalopathy in patients with AIDS. In this study, a possible gene therapy strategy for GBM using JCPyV virus-like particles (VLPs) as a gene delivery vector was investigated. We found that JCPyV VLPs were able to deliver the GFP reporter gene into tumor cells (U87-MG) for expression...
February 2, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29393186/antiangiogenic-therapy-of-high-grade-gliomas
#8
Jasmin Jo, Patrick Y Wen
Angiogenesis plays a critical pathologic role in malignant gliomas. In the past few years, numerous studies using bevacizumab (BEV), a humanized monoclonal antibody against vascular endothelial growth factor (VEGF), have been conducted in patients with brain tumors. Current evidence suggests that such treatment produces favorable results in patients with recurrent glioblastoma multiforme (GBM), but is not associated with any benefits in newly diagnosed GBM and recurrent WHO grade III gliomas. Initial experience using BEV for management of central nervous system radiation necrosis demonstrated radiographic improvement in the majority of cases, but optimal dose and treatment duration in such cases still remain in question...
2018: Progress in Neurological Surgery
https://www.readbyqxmd.com/read/29387926/glioblastoma-multiforme-another-potential-application-for-68ga-psma-pet-ct-as-a-guide-for-targeted-therapy
#9
Jolanta Kunikowska, Królicki Bartosz, Królicki Leszek
No abstract text is available yet for this article.
January 31, 2018: European Journal of Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/29358738/kinin-b1-receptor-stimulation-promotes-invasion-and-is-involved-in-cell-cell-interaction-of-co-cultured-glioblastoma-and-mesenchymal-stem-cells
#10
Mona N Oliveira, Micheli M Pillat, Helena Motaln, Henning Ulrich, Tamara T Lah
Glioblastoma multiforme (GBM) represents the most lethal brain tumour, and these tumours have very limited treatment options. Mesenchymal stem cells (MSC) are considered as candidates for advanced cell therapies, due to their tropism towards GBM, possibly affecting their malignancy, thus also representing a potential therapeutic vector. Therefore, we aimed to compare the effects of bone-marrow-derived versus adipose-tissue-derived MSC (BM-/AT-MSC) on heterogeneous populations of tumour cells. This cells' interplay was addressed by the in-vitro two-dimensional (monolayer) and three-dimensional (spheroid) co-culture models, using U87 and U373 GBM cell lines, expressing genotypically different mesenchymal transcriptome profiles...
January 22, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29352318/temozolomide-induced-increase-of-tumorigenicity-can-be-diminished-by-targeting-of-mitochondria-in-in-vitro-models-of-patient-individual-glioblastoma
#11
Doreen William, Madlin Walther, Björn Schneider, Michael Linnebacher, Carl Friedrich Classen
Glioblastoma multiforme (GBM) is a highly heterogeneous and aggressive brain tumor with a dismal prognosis. Development of resistance towards cytostatic drugs like the GBM standard drug temozolomide is a severe problem in GBM treatment. One potential source of GBM relapse could be so called cancer stem like cells (CSCs). These represent an undifferentiated subpopulation of cells with high potential for tumor initiation. Furthermore, it has been shown that differentiated GBM cells can regain CSC properties when exposed to continuous temozolomide treatment in vitro...
2018: PloS One
https://www.readbyqxmd.com/read/29348889/metformin-and-temozolomide-a-synergic-option-to-overcome-resistance-in-glioblastoma-multiforme-models
#12
Silvia Valtorta, Alessia Lo Dico, Isabella Raccagni, Daniela Gaglio, Sara Belloli, Letterio S Politi, Cristina Martelli, Cecilia Diceglie, Marcella Bonanomi, Giulia Ercoli, Valentina Vaira, Luisa Ottobrini, Rosa Maria Moresco
Glioblastoma multiforme (GBM) is the most aggressive primary brain tumor with poor survival. Cytoreduction in association with radiotherapy and temozolomide (TMZ) is the standard therapy, but response is heterogeneous and life expectancy is limited. The combined use of chemotherapeutic agents with drugs targeting cell metabolism is becoming an interesting therapeutic option for cancer treatment. Here, we found that metformin (MET) enhances TMZ effect on TMZ-sensitive cell line (U251) and overcomes TMZ-resistance in T98G GBM cell line...
December 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29340013/the-small-molecule-si113-synergizes-with-mitotic-spindle-poisons-in-arresting-the-growth-of-human-glioblastoma-multiforme
#13
Claudia Abbruzzese, Giada Catalogna, Enzo Gallo, Simona di Martino, Anna M Mileo, Mariantonia Carosi, Vincenzo Dattilo, Silvia Schenone, Francesca Musumeci, Patrizia Lavia, Nicola Perrotti, Rosario Amato, Marco G Paggi
Glioblastoma multiforme (GBM) is the deadliest brain tumor. State-of-art GBM therapy often fails to ensure control of a disease characterized by high frequency of recurrences and progression. In search for novel therapeutic approaches, we assayed the effect of compounds from a cancer drug library on the ADF GBM cell line, establishing their elevated sensitivity to mitotic spindle poisons. Our previous work showed that the effectiveness of the spindle poison paclitaxel in inhibiting cancer cell growth was dependent on the expression of RANBP1, a regulatory target of the serine/threonine kinase SGK1...
December 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29338907/new-photodynamic-molecular-beacons-pmb-as-potential-cancer-targeted-agents-in-pdt
#14
Aurélie Stallivieri, Ludovic Colombeau, Jérôme Devy, Nicolas Etique, Carine Chaintreuil, Bauyrzhan Myrzakhmetov, Mathilde Achard, Francis Baros, Philippe Arnoux, Régis Vanderesse, Céline Frochot
Further improvements in Photodynamic therapy (PDT) necessitate that the dye targets more selectively tumour tissues or neovascularization than healthy cells. Different enzymes such as matrix metalloproteinases (MMPs) are overexpressed in tumour areas. Among these MMPs, gelatinases (MMP-2 and MMP-9) and its activator MMP-14 are known to play a key role in tumour angiogenesis and the growth of many cancers such as glioblastoma multiforme (GBM), an aggressive malignant tumour of the brain. These last years, the concept of photodynamic molecular beacons (PMB) became interesting for controlling the photosensitizer's ability to generate singlet oxygen (1O2) close to target biomolecules as MMPs...
December 24, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/29251531/micellar-formulations-of-crizotinib-and-dasatinib-in-the-management-of-glioblastoma-multiforme
#15
Khaled Greish, Anfal Jasim, Neha Parayath, Sara Abdelghany, Ali Alkhateeb, Sebastien Taurin, Hayley Nehoff
Glioblastoma multiforme (GBM) defies the currently practiced management of radiotherapy, chemotherapy and surgery and hence, it is associated with a high fatality rate with a median survival of 14.6 months. In our previous work investigating different tyrosine kinase inhibitors (TKIs), we established that a combination of Crizotinib and Dasatinib exerted the most potent effect on different GBM cell lines. In the current work, to improve targeted therapy at the site of the tumor and avoid systemic toxicity, we exploited the enhanced permeability and retention effect by designing micellar formulations of these two TKIs...
December 18, 2017: Journal of Drug Targeting
https://www.readbyqxmd.com/read/29242608/immunotherapies-for-malignant-glioma
#16
REVIEW
Vassiliki A Boussiotis, Alain Charest
Glioblastoma multiforme (GBM) is a highly malignant primary brain cancer with a dreadful overall survival and for which treatment options are limited. Recent breakthroughs in novel immune-related treatment strategies for cancer have spurred interests in usurping the power of the patient's immune system to recognize and eliminate GBM. Here, we discuss the unique properties of GBM's tumor microenvironment, the effects of GBM standard on care therapy on tumor-associated immune cells, and review several approaches aimed at therapeutically targeting the immune system for GBM treatment...
December 15, 2017: Oncogene
https://www.readbyqxmd.com/read/29239327/influence-of-vascular-endothelial-growth-factor-and-radiation-on-gap-junctional-intercellular-communication-in-glioblastoma-multiforme-cell-lines
#17
Reinhardt Krcek, Pauline Latzer, Irenäus Anton Adamietz, Helmut Bühler, Carsten Theiss
Glioblastoma multiforme (GBM) is a highly aggressive glial brain tumor with an unfavorable prognosis despite all current therapies including surgery, radiation and chemotherapy. One characteristic of this tumor is a strong synthesis of vascular endothelial growth factor (VEGF), an angiogenesis factor, followed by pronounced vascularization. VEGF became a target in the treatment of GBM, for example with bevacizumab or the tyrosine kinase inhibitor axitinib, which blocks VEGF receptors. To improve patients' prognosis, new targets in the treatment of GBM are under investigations...
November 2017: Neural Regeneration Research
https://www.readbyqxmd.com/read/29221175/trpm8-is-required-for-survival-and-radioresistance-of-glioblastoma-cells
#18
Dominik Klumpp, Stephanie C Frank, Lukas Klumpp, Efe C Sezgin, Marita Eckert, Lena Edalat, Martin Bastmeyer, Daniel Zips, Peter Ruth, Stephan M Huber
TRPM8 is a Ca2+-permeable nonselective cation channel belonging to the melastatin sub-group of the transient receptor potential (TRP) family. TRPM8 is aberrantly overexpressed in a variety of tumor entities including glioblastoma multiforme where it reportedly contributes to tumor invasion. The present study aimed to disclose further functions of TRPM8 in glioma biology in particular upon cell injury by ionizing radiation. To this end, TCGA data base was queried to expose the TRPM8 mRNA abundance in human glioblastoma specimens and immunoblotting was performed to analyze the TRPM8 protein abundance in primary cultures of human glioblastoma...
November 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29202181/targeted-nanocomplex-carrying-sirna-against-malat1-sensitizes-glioblastoma-to-temozolomide
#19
Sang-Soo Kim, Joe B Harford, Manish Moghe, Antonina Rait, Kathleen F Pirollo, Esther H Chang
Intrinsic therapeutic resistance especially in cancer stem cells (CSCs) together with extensive tumor cell infiltration and restricted permeation of the blood-brain barrier (BBB) by drugs may all contribute to the treatment failure in patients with glioblastoma multiforme (GBM). Accumulating evidence suggests that long non-coding RNA (lncRNA), metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) plays a role in tumor cell infiltration and therapeutic resistance of GBM. Using our tumor-targeted nanocomplex, we have modulated the expression of MALAT1 and investigated its impact on GBM cells...
November 30, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29185191/delivery-of-exogenous-mir-124-to-glioblastoma-multiform-cells-by-wharton-s-jelly-mesenchymal-stem-cells-decreases-cell-proliferation-and-migration-and-confers-chemosensitivity
#20
S Sharif, M H Ghahremani, M Soleimani
MicroRNAs (miRs) are potential therapeutic targets in glioblastoma multiforme (GBM), but the difficulties associated with their delivery to tumor target cells have hampered their widespread use. Mesenchymal stem cells (MSCs) can migrate to the sites of cancers, including GBM and exert anti-tumor effects. In this study, it is shown that Wharton's jelly-MSCs (WJ-MSCs) have the ability to deliver exogenous miRs to GBM cells and the functional impact of this delivery is characterized. It is found that the labeled miR-124, as an example for miR of interest, can be successfully delivered with WJ-MSCs to U87 GBM cells via dependent or exosome-independent processes...
November 28, 2017: Stem Cell Reviews
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