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targeted therapy for glioblastoma multiforme

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https://www.readbyqxmd.com/read/28804551/a-tumor-suppressive-microrna-mirna-485-5p-inhibits-glioma-cell-proliferation-and-invasion-by-down-regulating-tpd52l2
#1
Jin Yu, Shi-Wen Wu, Wei-Ping Wu
Glioblastoma multiforme is the most deadly primary brain tumor and has no effective treatment. Therefore, it is important to identify novel and effective therapies that impede glioma tumorigenesis. MicroRNAs (miRNAs) are helpful analytical biomarkers and may be useful targets for treating multiple human cancers. Previous reports suggest that miRNA-485-5p is dysregulated and contributes to tumorigenesis in some cancer types. Nevertheless, the biological role of miRNA-485-5p in glioma is not well understood. In this study, we demonstrated that miRNA-485-5p expression was reduced in gliomat issues and cell lines...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28765533/development-of-an-integrated-monte-carlo-model-for-glioblastoma-multiforme-treated-with-boron-neutron-capture-therapy
#2
Leyla Moghaddasi, Eva Bezak
Glioblastomas (GBM) are notorious for their high fatality rate. Boron Neutron Capture Therapy (BNCT) being a biochemically targeted type of radiotherapy is a potent modality for GBM. In the current work, a BNCT treatment modelling framework for GBM was developed. Optimal Clinical Target Volume (CTV) margins for GBM-BNCT and the BNCT efficacy have been investigated. The model integrated a cell-based dosimetry model, an in-house-developed epithermal neutron beam model and previously-developed Microscopic Extension Probability (MEP) model...
August 1, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28759011/phosphorylated-mtor-and-yap-serve-as-prognostic-markers-and-therapeutic-targets-in-gliomas
#3
Mei Liu, Yong Lin, Xian-Chao Zhang, Yu-Huan Tan, Yue-Liang Yao, Juan Tan, Xia Zhang, You-Hong Cui, Xindong Liu, Yan Wang, Xiu-Wu Bian
Glioma is the most prevalent type of tumor in the brain and is comprised of grades I-IV, according to the WHO classification system. Grade IV glioma is also known as glioblastoma multiforme (GBM), the most malignant type of glioma. Glioma is characterized by a complex molecular background, and gene profiling studies have disclosed critical genetic events in human gliomas, which make targeted therapies the most promising therapeutic strategy. However, crosstalk between the targeted signaling pathways may hinder the efficacy of targeted therapies in gliomas...
July 31, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28753575/glioblastoma-and-glioblastoma-stem-cells-are-dependent-on-functional-mth1
#4
Linda Pudelko, Pegah Rouhi, Kumar Sanjiv, Helge Gad, Christina Kalderén, Andreas Höglund, Massimo Squatrito, Alberto J Schuhmacher, Steven Edwards, Daniel Hägerstrand, Ulrika Warpman Berglund, Thomas Helleday, Lars Bräutigam
Glioblastoma multiforme (GBM) is an aggressive form of brain cancer with poor prognosis. Cancer cells are characterized by a specific redox environment that adjusts metabolism to its specific needs and allows the tumor to grow and metastasize. As a consequence, cancer cells and especially GBM cells suffer from elevated oxidative pressure which requires antioxidant-defense and other sanitation enzymes to be upregulated. MTH1, which degrades oxidized nucleotides, is one of these defense enzymes and represents a promising cancer target...
July 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/28752098/recombinant-immunotoxin-therapy-of-glioblastoma-smart-design-key-findings-and-specific-challenges
#5
REVIEW
Shaowei Zhu, Yuanyi Liu, Paul C Wang, Xinbin Gu, Liang Shan
Recombinant immunotoxins (RITs) refer to a group of recombinant protein-based therapeutics, which consists of two components: an antibody variable fragment or a specific ligand that allows RITs to bind specifically to target cells and an engineered toxin fragment that kills the target cells upon internalization. To date, over 1,000 RITs have been generated and significant success has been achieved in the therapy of hematological malignancies. However, the immunogenicity and off-target toxicities of RITs remain as significant barriers for their application to solid tumor therapy...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28729027/micrornas-as-multifaceted-players-in-glioblastoma-multiforme
#6
Neri Mercatelli, Silvia Galardi, Silvia Anna Ciafrè
Glioblastoma multiforme (GBM) is the most common and inevitably lethal primary brain tumor, with a median survival rate of only 15 months from diagnosis. The current standard treatment involves maximal surgical resection flanked by radiotherapy and chemotherapy with the alkylating agent temozolomide. However, even such aggressive treatment is never curative, and recurrent tumors always arise, commonly in more aggressive, chemo- and radio-resistant forms, leading to untreatable and deadly tumors. MicroRNAs, recognized major players in cancer, are deeply involved in GBM, as shown by more than a decade of studies...
2017: International Review of Cell and Molecular Biology
https://www.readbyqxmd.com/read/28706148/expression-differences-of-programmed-death-ligand-1-in-de-novo-and-recurrent-glioblastoma-multiforme
#7
Sabrina Heynckes, Annette Gaebelein, Gerrit Haaker, Jürgen Grauvogel, Pamela Franco, Irina Mader, Maria Stella Carro, Marco Prinz, Daniel Delev, Oliver Schnell, Dieter Henrik Heiland
The biology of recurrent glioblastoma multiforme (GBM) is a dynamic process influenced by selection pressure induced by different antitumoural therapies. The poor clinical outcome of tumours in the recurrent stage necessitates the development of effective therapeutic strategies. Checkpoint-inhibition (PD1/PD-L1 Inhibition) is a hallmark of immunotherapy being investigated in ongoing clinical trials. The purpose of this study was to analyse the PD-L1 expression in de-novo and recurrent glioblastoma multiforme and to explore associated genetic alterations and clinical traits...
June 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28670499/wnt-signaling-pathway-protein-lef1-in-cancer-as-a-biomarker-for-prognosis-and-a-target-for-treatment
#8
REVIEW
Larion Santiago, Garrett Daniels, Dongwen Wang, Fang-Ming Deng, Peng Lee
Transcription factors are regulatory proteins that either activate or repress the transcription of genes via binding to DNA regulatory sequences and regulating recruitment of transcriptional complexes. Lymphoid enhancer-binding factor 1 (LEF1), a member of the T-cell Factor (TCF)/LEF1 family of high-mobility group transcription factors, is a downstream mediator of the Wnt/β-catenin signaling pathway, but can also modulate gene transcription independently. LEF1 is essential in stem cell maintenance and organ development, especially in its role in epithelial-mesenchymal transition (EMT) by activating the transcription of hallmark EMT effectors including N-Cadherin, Vimentin, and Snail...
2017: American Journal of Cancer Research
https://www.readbyqxmd.com/read/28656206/nicotinic-acid-impairs-assembly-of-leading-edge-in-glioma-cells
#9
Xiangcai Yang, Shuting Mei, Hua Niu, Jiejing Li
Malignant glioma is a clinically formidable disease. It commonly leads to death within 5 years after diagnosis. Physicians are often baffled since the inevitable diffuse invasion deteriorates clinical outcomes rapidly. Therefore, cancerous infiltration presents a foremost challenge to all therapeutic strategies on glioblastoma multiforme (GBM). Previously, we demonstrated that nicotinic acid (NA) possesses a brand new function by targeting F-actin stress fibers. By treating HEK293 or NIH3T3 cells with a certain concentration of NA, the F-actin stress fiber was significantly disassembled...
June 27, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28649003/targeting-egfrviii-for-glioblastoma-multiforme
#10
Ju Yang, Jing Yan, Baorui Liu
Glioblastoma multiforme (GBM) is the most progressive primary brain tumor. Targeting a novel and highly specific tumor antigen is one of the strategies to overcome tumors. EGFR variant III (EGFRvIII) is present in 25%-33% of all patients with GBM and is exclusively expressed on tumor tissue cells. Currently, there are various approaches to target EGFRvIII, including CAR T-cell therapy, therapeutic vaccines, antibodies, and Bi-specific T Cell Engager. In this review, we focus on the preclinical and clinical findings of targeting EGFRvIII for GBM...
June 23, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28634226/phostine-pst3-1a-targets-mgat5-and-inhibits-glioblastoma-initiating-cell-invasiveness-and-proliferation
#11
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/28629170/egfr-and-egfrviii-promote-angiogenesis-and-cell-invasion-in-glioblastoma-combination-therapies-for-an-effective-treatment
#12
REVIEW
Stefanie Keller, Mirko H H Schmidt
Epidermal growth factor receptor (EGFR) and the mutant EGFRvIII are major focal points in current concepts of targeted cancer therapy for glioblastoma multiforme (GBM), the most malignant primary brain tumor. The receptors participate in the key processes of tumor cell invasion and tumor-related angiogenesis and their upregulation correlates with the poor prognosis of glioma patients. Glioma cell invasion and increased angiogenesis share mechanisms of the degradation of the extracellular matrix (ECM) through upregulation of ECM-degrading proteases as well as the activation of aberrant signaling pathways...
June 18, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28620939/engineering-novel-targeted-boron-10-enriched-theranostic-nanomedicine-to-combat-against-murine-brain-tumors-via-mr-imaging-guided-boron-neutron-capture-therapy
#13
Naresh Kuthala, Raviraj Vankayala, Yi-Nan Li, Chi-Shiun Chiang, Kuo Chu Hwang
Glioblastoma multiforme (GBM) is a very common type of "incurable" malignant brain tumor. Although many treatment options are currently available, most of them eventually fail due to its recurrence. Boron neutron capture therapy (BNCT) emerges as an alternative noninvasive therapeutic treatment modality. The major challenge in treating GBMs using BNCT is to achieve selective imaging, targeting, and sufficient accumulation of boron-containing drug at the tumor site so that effective destruction of tumor cells can be achieved without harming the normal brain cells...
June 16, 2017: Advanced Materials
https://www.readbyqxmd.com/read/28610419/gene-expression-profiling-of-chemokines-and-their-receptors-in-low-and-high-grade-astrocytoma
#14
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/28602756/antrodia-cinnamomea-sensitizes-radio-chemo-therapy-of-cancer-stem-like-cells-by-modulating-microrna-expression
#15
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/28602411/survival-outcomes-of-elderly-patients-with-glioblastoma-multiforme-in-their-75th-year-or-older-treated-with-adjuvant-therapy
#16
Georgia Harris, Dasantha Jayamanne, Helen Wheeler, Cecelia Gzell, Marina Kastelan, Geoff Schembri, David Brazier, Raymond Cook, Jonathan Parkinson, Mustafa Khasraw, Sandra Louw, Michael Back
PURPOSE: To assess the outcomes of the most elderly cohort of patients with a diagnosis of glioblastoma multiforme (GBM) after intensity modulated radiation therapy (IMRT). METHODS AND MATERIALS: The data of patients with GBM who had underwent IMRT from May 2007 to December 2015 were entered into a prospective database. Analysis was performed on the data from patients diagnosed during or after 75 years of age. The primary endpoint was the median survival. Univariate and multivariate analyses were performed with respect to survival for patients aged 74 to 80 versus >80 years, Eastern Cooperative Oncology Group performance status of 0 to 1 versus 2 to 3, extent of resection, a high radiation dose (60 Gy) versus any hypofractionated schedule, MGMT methylation status, planning target volume, and the use of temozolomide (TMZ) versus no TMZ...
July 15, 2017: International Journal of Radiation Oncology, Biology, Physics
https://www.readbyqxmd.com/read/28593138/licochalcone-a-specifically-induces-cell-death-in-glioma-stem-cells-via-mitochondrial-dysfunction
#17
Kenta Kuramoto, Shuhei Suzuki, Hirotsugu Sakaki, Hiroyuki Takeda, Tomomi Sanomachi, Shizuka Seino, Yoshitaka Narita, Takamasa Kayama, Chifumi Kitanaka, Masashi Okada
Glioblastoma multiforme is the most malignant primary intrinsic brain tumor. Glioma stem cells (GSCs) are associated with chemoradiotherapy resistance and the recurrence of glioblastomas after conventional therapy. The targeting of GSCs is potentially an effective treatment for the long-term survival of glioblastoma patients. Licochalcone A, a natural chalconoid from licorice root, exerts anticancer effects; however, its effect on GSCs remains unknown. We found that Licochalcone A induced massive caspase-dependent death in GSCs but not in differentiated GSCs nor normal somatic and neural stem cells...
June 2017: FEBS Open Bio
https://www.readbyqxmd.com/read/28592260/recent-advances-in-the-use-of-pi3k-inhibitors-for-glioblastoma-multiforme-current-preclinical-and-clinical-development
#18
REVIEW
Hua-Fu Zhao, Jing Wang, Wei Shao, Chang-Peng Wu, Zhong-Ping Chen, Shing-Shun Tony To, Wei-Ping Li
Glioblastoma multiforme (GBM) is the most common and aggressive malignant primary tumor in the central nervous system. One of the most widely used chemotherapeutic drugs for GBM is temozolomide, which is a DNA-alkylating agent and its efficacy is dependent on MGMT methylation status. Little progress in improving the prognosis of GBM patients has been made in the past ten years, urging the development of more effective molecular targeted therapies. Hyper-activation of the phosphatidylinositol 3-kinase (PI3K)/Akt pathway is frequently found in a variety of cancers including GBM, and it plays a central role in the regulation of tumor cell survival, growth, motility, angiogenesis and metabolism...
June 7, 2017: Molecular Cancer
https://www.readbyqxmd.com/read/28591726/multifunctional-targeted-liposomal-drug-delivery-for-efficient-glioblastoma-treatment
#19
Zakia Belhadj, Changyou Zhan, Man Ying, Xiaoli Wei, Cao Xie, Zhiqiang Yan, Weiyue Lu
Glioblastoma multiforme (GBM) has been considered to be the most malignant brain tumors. Due to the existence of various barriers including the blood-brain barrier (BBB) and blood-brain tumor barrier (BBTB) greatly hinder the accumulation and deep penetration of chemotherapeutics, the treatment of glioma remains to be the most challenging task in clinic. In order to circumvent these hurdles, we developed a multifunctional liposomal glioma-targeted drug delivery system (c(RGDyK)/pHA-LS) modified with cyclic RGD (c(RGDyK)) and p-hydroxybenzoic acid (pHA) in which c(RGDyK) could target integrin αvβ3 overexpressed on the BBTB and glioma cells and pHA could target dopamine receptors on the BBB...
May 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28581412/dosimetric-impact-of-using-a-virtual-couch-shift-for-online-correction-of-setup-errors-for-brain-patients-on-an-integrated-high-field-magnetic-resonance-imaging-linear-accelerator
#20
Mark Ruschin, Arjun Sahgal, Chia-Lin Tseng, Marcus Sonier, Brian Keller, Young Lee
PURPOSE: To quantify the dosimetric impact of using virtual couch shift (VCS) for correcting setup errors in glioblastoma multiforme (GBM) patients treated on a magnetic resonance imaging (MRI)-linac. METHODS AND MATERIALS: Six GBM patients treated with 60 Gy (30 fractions) were selected for this simulation study. For each case, 2 reference plans were generated in the MRL treatment planning system: With (WIB) and with no (NOB) MRI B field present. Subsequently, 2-mm, 4-mm, and 6-mm translational errors were simulated and corrected for using a VCS method based on shift-only, warm start segment weight (SWO), and segment weight and shape (SSO) optimization...
July 1, 2017: International Journal of Radiation Oncology, Biology, Physics
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