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targeted therapy for glioblastoma multiforme

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https://www.readbyqxmd.com/read/28978003/multifunctional-targeted-liposomal-drug-delivery-for-efficient-glioblastoma-treatment
#1
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...
September 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28950062/integrating-transcriptomic-data-with-mechanistic-systems-pharmacology-models-for-virtual-drug-combination-trials
#2
Anne Marie Barrette, Mehdi Bouhaddou, Marc R Birtwistle
Monotherapy clinical trials with mutation-targeted kinase inhibitors, despite some success in other cancers, have yet to impact glioblastoma (GBM). Besides insufficient blood-brain barrier penetration, combinations are key to overcoming obstacles such as intratumoral heterogeneity, adaptive resistance, and the epistatic nature of tumor genomics that cause mutation-targeted therapies to fail. With now hundreds of potential drugs, exploring the combination space clinically and preclinically is daunting. We are building a simulation-based approach that integrates patient-specific data with a mechanistic computational model of pan-cancer driver pathways (receptor tyrosine kinases, RAS/RAF/ERK, PI3K/AKT/mTOR, cell cycle, apoptosis, and DNA damage) to prioritize drug combinations by their simulated effects on tumor cell proliferation and death...
October 6, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28922698/survival-improvements-with-adjuvant-therapy-in-patients-with-glioblastoma
#3
Dasantha Jayamanne, Helen Wheeler, Raymond Cook, Charles Teo, David Brazier, Geoff Schembri, Marina Kastelan, Linxin Guo, Michael F Back
BACKGROUND: Evaluate survival of patients diagnosed with glioblastoma multiforme (GBM) managed with adjuvant intensity modulated radiation therapy and temozolomide since the introduction of the European Organisation for Research and Treatment of Cancer and National Cancer Institute of Canada Clinical Trials Group (EORTC-NCIC) protocol. METHODS: All patients with GBM managed between May 2007 and December 2014 with EORTC-NCIC protocol were entered into a prospective database...
September 18, 2017: ANZ Journal of Surgery
https://www.readbyqxmd.com/read/28901390/microrna-132-induces-temozolomide-resistance-and-promotes-the-formation-of-cancer-stem-cell-phenotypes-by-targeting-tumor-suppressor-candidate%C3%A2-3-in-glioblastoma
#4
Zhen-Xiu Cheng, Wen-Bo Yin, Zhong-Yu Wang
The prognosis of patients suffering from glioblastoma [also referred to as glioblastoma multiforme (GBM)] is dismal despite multimodal therapy. Chemotherapy with temozolomide may suppress tumor growth for a certain period of time (a few months); however, invariable tumor recurrence suggests that glioblastoma initiating cells (GICs) render these tumors persistant. Thus, the understanding of the molecular mechanisms of action of GICs as regards their role in the progression of GBM is important as such knowledge will be helpful in the discovery of novel drug targets, as well as in the design of novel therapeutic strategies for more effective treatment of the disease...
November 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28888921/n-4-b-4-4-5-5-tetramethyl-1-3-2-dioxaborolan-methyl-2-deoxycytidine-as-a-potential-boron-delivery-agent-with-respect-to-glioblastoma
#5
Łukasz Uram, Joanna Nizioł, Piotr Maj, Justyna Sobich, Wojciech Rode, Tomasz Ruman
Glioblastoma multiforme (GBM) is a central nervous system tumor of grade IV, according to the WHO classification, extremely resistant to all currently used forms of therapy, including resection, radiotherapy, chemotherapy or combined therapy. Therefore, more effective treatment strategies of this tumor are needed, with boron neutron capture therapy (BNCT) being a potential solution, provided a proper cancer cells-targeted 10B delivery agent is found. In search of such an agent, toxicity and capacity to target DNA of a boronated derivative of 2'-deoxycytidine, N(4)-[B-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan)methyl]-2'-deoxycytidine (1), was tested against human tumor vs...
September 7, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28886331/towards-carborane-functionalised-structures-for-the-treatment-of-brain-cancer
#6
REVIEW
Gianpiero Calabrese, Anis Daou, Eugen Barbu, John Tsibouklis
Boron neutron capture therapy (BNCT) is a promising targeted chemoradiotherapeutic technique for the management of invasive brain tumors, such as glioblastoma multiforme (GBM). A prerequisite for effective BNCT is the selective targeting of tumour cells with (10)B-rich therapeutic moieties. To this end, polyhedral boranes, especially carboranes, have received considerable attention because they combine a high boron content with relative low toxicity and metabolic inertness. Here, we review progress in the molecular design of recently investigated carborane derivatives in light of the widely accepted performance requirements for effective BNCT...
September 5, 2017: Drug Discovery Today
https://www.readbyqxmd.com/read/28879167/vascular-endothelial-growth-factor-irradiation-and-axitinib-have-diverse-effects-on-motility-and-proliferation-of-glioblastoma-multiforme-cells
#7
Reinhardt Krcek, Veronika Matschke, Verena Theis, Irenäus Anton Adamietz, Helmut Bühler, Carsten Theiss
Glioblastoma multiforme (GBM) is the most common primary brain tumor. It is highly aggressive with an unfavorable prognosis for the patients despite therapies including surgery, irradiation, and chemotherapy. One important characteristic of highly vascularized GBM is the strong expression of vascular endothelial growth factor (VEGF). VEGF has become a new target in the treatment of GBM, and targeted therapies such as the VEGF-receptor blocker axitinib are in clinical trials. Most studies focus on VEGF-induced angiogenesis, but only very few investigations analyze autocrine or paracrine effects of VEGF on the tumor cells...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28864225/rna-interference-for-glioblastoma-therapy-innovation-ladder-from-the-bench-to-clinical-trials
#8
REVIEW
Eunice L Lozada-Delgado, Nilmary Grafals-Ruiz, Pablo E Vivas-Mejía
Glioblastoma multiforme (GBM) is the most common and deadliest type of primary brain tumor with a prognosis of 14months after diagnosis. Current treatment for GBM patients includes "total" tumor resection, temozolomide-based chemotherapy, radiotherapy or a combination of these options. Although, several targeted therapies, gene therapy, and immunotherapy are currently in the clinic and/or in clinical trials, the overall survival of GBM patients has hardly improved over the last two decades. Therefore, novel multitarget modalities are urgently needed...
November 1, 2017: Life Sciences
https://www.readbyqxmd.com/read/28840962/biomarkers-and-therapeutic-advances-in-glioblastoma-multiforme
#9
Andrew Octavian Sasmita, Ying Pei Wong, Anna Pick Kiong Ling
Glioblastoma multiforme (GBM) is a malignant tumor within the brain. Generally classified as primary and secondary with several different subtypes, ample molecular biomarkers have risen throughout the years which have garnered the attention of researchers. The advancements in genomics and proteomics have allowed researchers to gather prominent molecular biomarkers. All these biomarkers are gathered by means of biopsy or bodily fluid sample collection and are quantitatively analyzed by polymerase chain reaction coupled with other computational technologies...
August 25, 2017: Asia-Pacific Journal of Clinical Oncology
https://www.readbyqxmd.com/read/28823025/nanomedicine-associated-with-photodynamic-therapy-for-glioblastoma-treatment
#10
REVIEW
Leonardo B de Paula, Fernando L Primo, Antonio C Tedesco
Glioblastoma, also known as glioblastoma multiforme (GBM), is the most recurrent and malignant astrocytic glioma found in adults. Biologically, GBMs are highly aggressive tumors that often show diffuse infiltration of the brain parenchyma, making complete surgical resection difficult. GBM is not curable with surgery alone because tumor cells typically invade the surrounding brain, rendering complete resection unsafe. Consequently, present-day therapy for malignant glioma remains a great challenge. The location of the invasive tumor cells presents several barriers to therapeutic delivery...
August 19, 2017: Biophysical Reviews
https://www.readbyqxmd.com/read/28804551/a-tumor-suppressive-microrna-mirna-485-5p-inhibits-glioma-cell-proliferation-and-invasion-by-down-regulating-tpd52l2
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
REVIEW
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...
September 10, 2017: Cancer Letters
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