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targeted therapy for glioblastoma multiforme

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https://www.readbyqxmd.com/read/28649003/targeting-egfrviii-for-glioblastoma-multiforme
#1
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 22, 2017: Cancer Letters
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/28629170/egfr-and-egfrviii-promote-angiogenesis-and-cell-invasion-in-glioblastoma-combination-therapies-for-an-effective-treatment
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
https://www.readbyqxmd.com/read/28576716/enhanced-targeting-of-invasive-glioblastoma-cells-by-peptide-functionalized-gold-nanorods-in-hydrogel-based-3d-cultures
#12
Diana P N Gonçalves, Raul D Rodriguez, Thomas Kurth, Laura J Bray, Marcus Binner, Christiane Jungnickel, Fatih N Gür, Steve W Poser, Thorsten L Schmidt, Dietrich R T Zahn, Andreas Androutsellis-Theotokis, Michael Schlierf, Carsten Werner
Cancer stem cells (CSCs) are responsible for drug resistance, tumor recurrence, and metastasis in several cancer types, making their eradication a primary objective in cancer therapy. Glioblastoma Multiforme (GBM) tumors are usually composed of a highly infiltrating CSC subpopulation, which has Nestin as a putative marker. Since the majority of these infiltrating cells are able to elude conventional therapies, we have developed gold nanorods (AuNRs) functionalized with an engineered peptide capable of specific recognition and selective eradication of Nestin positive infiltrating GBM-CSCs...
May 30, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28559975/inhibition-of-glioblastoma-growth-and-invasion-by-125-i-brachytherapy-in-rat-glioma-model
#13
Feihong Chen, Dan Wang
Development of the novel targeted therapies for glioblastoma multiforme is very important. Brachytherapy has been proven to provide a good alternative to surgical removal of the prostate, breast and cervix with reduced risk of certain long-term side effects. Thus, (125)I brachytherapy was used to effect on the growth and invasion of glioma cells in vitro and in vivo. The inhibitory effect of (125)I seeds on C6 cells proliferation was determined by MTT assay. A rat intracranial glioma model was established and the (125)I seeds were implanted into the glioma area...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28542439/host-mediated-inflammatory-influence-on-glioblastoma-multiforme-recurrence-following-high-dose-ionizing-radiation
#14
J Tyson McDonald, Xuefeng Gao, Cole Steber, Jawon Lee Breed, Caitlin Pollock, Lili Ma, Lynn Hlatky
Despite optimal clinical treatment, glioblastoma multiforme (GBM) inevitably recurs. Standard treatment of GBM, exposes patients to radiation which kills tumor cells, but also modulates the molecular fingerprint of any surviving tumor cells and the cross-talk between those cells and the host. Considerable investigation of short-term (hours to days) post-irradiation tumor cell response has been undertaken, yet long-term responses (weeks to months) which are potentially even more informative of recurrence, have been largely overlooked...
2017: PloS One
https://www.readbyqxmd.com/read/28534507/cecr1-mediated-cross-talk-between-macrophages-and-vascular-mural-cells-promotes-neovascularization-in-malignant-glioma
#15
C Zhu, I Chrifi, D Mustafa, M van der Weiden, P J M Leenen, D J Duncker, J M Kros, C Cheng
Glioblastomas (glioblastoma multiforme, GBM) are most malignant brain tumors characterized by profound vascularization. The activation of macrophages strongly contributes to tumor angiogenesis during GBM development. Previously, we showed that extracellular adenosine deaminase protein Cat Eye Syndrome Critical Region Protein 1 (CECR1) is highly expressed by M2-like macrophages in GBM where it defines macrophage M2 polarization and contributes to tumor expansion. In this study, the effect of CECR1 in macrophages on tumor angiogenesis was investigated...
May 22, 2017: Oncogene
https://www.readbyqxmd.com/read/28494176/comparative-analysis-of-the-effects-of-a-sphingosine-kinase-inhibitor-to-temozolomide-and-radiation-treatment-on-glioblastoma-cell-lines
#16
Liliana R Oancea-Castillo, Carmen Klein, Amir Abdollahi, Klaus-Josef Weber, Anne Régnier-Vigouroux, Ivana Dokic
Glioblastoma multiforme (GBM) exhibits high resistance to the standard treatment of temozolomide (TMZ) combined with radiotherapy, due to its remarkable cell heterogeneity. Accordingly, there is a need to target alternative molecules enhancing specific GBM autocrine or paracrine mechanisms and amplifying the effect of standard treatment. Sphingosine 1-phosphate (S1P) is such a lipid target molecule with an important role in cell invasion and proliferation. Sphingosine kinase inhibitors (SKI) prevent S1P formation and induce increased production of reactive oxygen species (ROS), which may potentiate radiation cytotoxicity...
May 11, 2017: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/28484222/in-silico-evaluation-of-dna-damage-inducible-transcript-4-gene-ddit4-as-prognostic-biomarker-in-several-malignancies
#17
Joseph A Pinto, Christian Rolfo, Luis E Raez, Alexandra Prado, Jhajaira M Araujo, Leny Bravo, Williams Fajardo, Zaida D Morante, Alfredo Aguilar, Silvia P Neciosup, Luis A Mas, Denisse Bretel, Justin M Balko, Henry L Gomez
DDIT4 gene encodes a protein whose main action is to inhibit mTOR under stress conditions whilst several in vitro studies indicate that its expression favors cancer progression. We have previously described that DDIT4 expression is an independent prognostic factor for tripe negative breast cancer resistant to neoadjuvant chemotherapy. We herein report that high DDIT4 expression is related to the outcome (recurrence-free survival, time to progression and overall survival) in several cancer types. We performed in silico analysis in online platforms, in pooled datasets from KM Plotter and meta-analysis of individual datasets from SurvExpress...
May 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28483513/crgd-peptide-installed-epirubicin-loaded-polymeric-micelles-for-effective-targeted-therapy-against-brain-tumors
#18
S Quader, X Liu, Y Chen, P Mi, T Chida, T Ishii, Y Miura, N Nishiyama, H Cabral, K Kataoka
Current therapeutic strategies against glioblastoma multiforme (GBM) are futile mainly because of the poor access of drugs into malignant tissues, which is hindered by the tight blood-brain tumor barrier in the GBM vasculature. Nanomedicines have shown potential for circumventing the vascular barriers of GBM, particularly by targeting markers on the luminal side of endothelial cells in the blood vessels of GBM for achieving effective and selective translocation into the tumor. Thus, as the αvβ3 and αvβ5 integrins overexpressed on the endothelial cells of GBM can be targeted by cyclic-Arg-Gly-Asp (cRGD) peptide, herein, we developed cRGD-installed micellar nanomedicines loading epirubicin, the potent antiglioblastoma agent, through a pH-sensitive hydrazone-bond for effective treatment of GBM...
July 28, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28464840/sparing-of-normal-tissues-with-volumetric-arc-radiation-therapy-for-glioblastoma-single-institution-clinical-experience
#19
Tina Marie Briere, Mary Frances McAleer, Lawrence B Levy, James N Yang
BACKGROUND: Patients with glioblastoma multiforme (GBM) require radiotherapy as part of definitive management. Our institution has adopted the use of volumetric arc therapy (VMAT) due to superior sparing of the adjacent organs at risk (OARs) compared to intensity modulated radiation therapy (IMRT). Here we report our clinical experience by analyzing target coverage and sparing of OARs for 90 clinical treatment plans. METHODS: VMAT and IMRT patient cohorts comprising 45 patients each were included in this study...
May 2, 2017: Radiation Oncology
https://www.readbyqxmd.com/read/28459461/mir-181b-modulates-egfr-dependent-vcam-1-expression-and-monocyte-adhesion-in-glioblastoma
#20
Y-S Liu, H-Y Lin, S-W Lai, C-Y Huang, B-R Huang, P-Y Chen, K-C Wei, D-Y Lu
Tumor-associated macrophages (TAMs) originate as circulating monocytes, and are recruited to gliomas, where they facilitate tumor growth and migration. Understanding the interaction between TAM and cancer cells may identify therapeutic targets for glioblastoma multiforme (GBM). Vascular cell adhesion molecule-1 (VCAM-1) is a cytokine-induced adhesion molecule expressed on the surface of cancer cells, which is involved in interactions with immune cells. Analysis of the glioma patient database and tissue immunohistochemistry showed that VCAM-1 expression correlated with the clinico-pathological grade of gliomas...
May 1, 2017: Oncogene
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