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https://www.readbyqxmd.com/read/29700310/focused-ultrasound-enabled-brain-tumor-liquid-biopsy
#1
Lifei Zhu, Galen Cheng, Dezhuang Ye, Arash Nazeri, Yimei Yue, Weijun Liu, Xiaowei Wang, Gavin P Dunn, Allegra A Petti, Eric C Leuthardt, Hong Chen
Although blood-based liquid biopsies have emerged as a promising non-invasive method to detect biomarkers in various cancers, limited progress has been made for brain tumors. One major obstacle is the blood-brain barrier (BBB), which hinders efficient passage of tumor biomarkers into the peripheral circulation. The objective of this study was to determine whether FUS in combination with microbubbles can enhance the release of biomarkers from the brain tumor to the blood circulation. Two glioblastoma tumor models (U87 and GL261), developed by intracranial injection of respective enhanced green fluorescent protein (eGFP)-transduced glioblastoma cells, were treated by FUS in the presence of systemically injected microbubbles...
April 26, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29524243/toward-a-noninvasive-estimate-of-interstitial-fluid-pressure-by-dynamic-contrast-enhanced-mri-in-a-rat-model-of-cerebral-tumor
#2
Rasha Elmghirbi, Tavarekere N Nagaraja, Stephen L Brown, Kelly A Keenan, Swayamprava Panda, Glauber Cabral, Hassan Bagher-Ebadian, George W Divine, Ian Y Lee, James R Ewing
PURPOSE: This study demonstrates a DCE-MRI estimate of tumor interstitial fluid pressure (TIFP) and hydraulic conductivity in a rat model of glioblastoma, with validation against an invasive wick-in-needle (WIN) technique. An elevated TIFP is considered a mark of aggressiveness, and a decreased TIFP a predictor of response to therapy. METHODS: The DCE-MRI studies were conducted in 36 athymic rats (controls and posttreatment animals) with implanted U251 cerebral tumors, and with TIFP measured using a WIN method...
March 9, 2018: Magnetic Resonance in Medicine: Official Journal of the Society of Magnetic Resonance in Medicine
https://www.readbyqxmd.com/read/29487696/the-evolutionary-pattern-of-mutations-in-glioblastoma-reveals-therapy-mediated-selection
#3
Andrea M Muscat, Nicholas C Wong, Katharine J Drummond, Elizabeth M Algar, Mustafa Khasraw, Roel Verhaak, Kathryn Field, Mark A Rosenthal, David M Ashley
Glioblastoma presents as a heterogeneous disease with poor prognosis despite the use of multimodal therapy. Analysis of genomic DNA changes between initial diagnosis and recurrence in response to standard treatment protocols would enhance understanding of disease progression and better inform new treatment strategies. A cohort of 21 patients with primary glioblastoma were examined between diagnosis and first recurrence. This study presented a rare opportunity to characterize molecular alterations in tumors observed in three patients who received no therapeutic intervention, other than surgery, offering a unique control...
January 30, 2018: Oncotarget
https://www.readbyqxmd.com/read/29472310/temozolomide-plus-bevacizumab-in-elderly-patients-with-newly-diagnosed-glioblastoma-and-poor-performance-status-an-anocef-phase-ii-trial-atag
#4
Germán Reyes-Botero, Stéphanie Cartalat-Carel, Olivier L Chinot, Maryline Barrie, Luc Taillandier, Patrick Beauchesne, Isabelle Catry-Thomas, Jérôme Barrière, Jean-Sebastien Guillamo, Michel Fabbro, Didier Frappaz, Alexandra Benouaich-Amiel, Emilie Le Rhun, Chantal Campello, Isabelle Tennevet, François Ghiringhelli, Marie-Laure Tanguy, Karima Mokhtari, Jérôme Honnorat, Jean-Yves Delattre
LESSONS LEARNED: Results suggest that the combination of bevacizumab plus temozolomide is active in terms of response rate, survival, performance, quality of life, and cognition in elderly patients with glioblastoma multiforme with poor performance status.Whether this combination is superior to temozolomide alone remains to be demonstrated by a randomized study. BACKGROUND: The optimal treatment of glioblastoma multiforme (GBM) in patients aged ≥70 years with a Karnofsky performance status (KPS) <70 is not established...
February 22, 2018: Oncologist
https://www.readbyqxmd.com/read/29431617/antisecretory-factor-mediated-inhibition-of-cell-volume-dynamics-produces-antitumor-activity-in-glioblastoma
#5
Shirin Ilkhanizadeh, Hanna Sabelström, Yekaterina A Miroshnikova, Aaron Frantz, Wen Zhu, Aurora Idilli, Jon N Lakins, Christin Schmidt, David A Quigley, Trenten Fenster, Edith Yuan, Jacqueline R Trzeciak, Supna Saxena, Olle R Lindberg, Janna K Mouw, Jason A Burdick, Sergey Magnitsky, Mitchel S Berger, Joanna J Phillips, Daniele Arosio, Dandan Sun, Valerie M Weaver, William A Weiss, Anders I Persson
Interstitial fluid pressure (IFP) presents a barrier to drug uptake in solid tumors, including the aggressive primary brain tumor glioblastoma (GBM). It remains unclear how fluid dynamics impacts tumor progression and can be targeted therapeutically. To address this issue, a novel telemetry-based approach was developed to measure changes in IFP during progression of GBM xenografts. Antisecretory factor (AF) is an endogenous protein that displays antisecretory effects in animals and patients. Here, endogenous induction of AF protein or exogenous administration of AF peptide reduced IFP and increased drug uptake in GBM xenografts...
May 2018: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29156675/glioblastoma-and-glioblastoma-stem-cells-are-dependent-on-functional-mth1
#6
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...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156557/the-invasive-region-of-glioblastoma-defined-by-5ala-guided-surgery-has-an-altered-cancer-stem-cell-marker-profile-compared-to-central-tumour
#7
Stuart J Smith, Mohammed Diksin, Saachi Chhaya, Shwetha Sairam, Maria A Estevez-Cebrero, Ruman Rahman
Glioblastoma, a WHO grade IV astrocytoma, is a highly aggressive and heterogeneous tumour that infiltrates deeply into surrounding brain parenchyma, making complete surgical resection impossible. Despite chemo-radiotherapy, the residual cell population within brain parenchyma post-surgery causes inevitable recurrence. Previously, the tumour core has been the focus of research and the basis for targeted therapeutic regimes, which have failed to improve survival in clinical trials. Here, we focus on the invasive margin as defined by the region with 5-aminolevulinic acid (5ALA) (GliolanTM) fluorescence at surgery beyond the T1 enhancing region on magnetic resonance imaging (MRI)...
November 18, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29124875/emerging-functions-of-the-egfr-in-cancer
#8
REVIEW
Sara Sigismund, Daniele Avanzato, Letizia Lanzetti
The physiological function of the epidermal growth factor receptor (EGFR) is to regulate epithelial tissue development and homeostasis. In pathological settings, mostly in lung and breast cancer and in glioblastoma, the EGFR is a driver of tumorigenesis. Inappropriate activation of the EGFR in cancer mainly results from amplification and point mutations at the genomic locus, but transcriptional upregulation or ligand overproduction due to autocrine/paracrine mechanisms has also been described. Moreover, the EGFR is increasingly recognized as a biomarker of resistance in tumors, as its amplification or secondary mutations have been found to arise under drug pressure...
January 2018: Molecular Oncology
https://www.readbyqxmd.com/read/29083237/a-new-protein-extract-inhibitor-from-hypobranchial-purple-gland-of-hexaplex-trunculus-a-mediterranean-mollusk-impairs-the-motility-of-human-glioblastoma-u87-and-the-hela-cell-line-of-cervical-carcinoma-cells
#9
Hazem Ben Mabrouk, Sayari Nejia, Morjen Maram, Marrakchi Naziha, Chabchoub-Ellouze Soufia
The aim of this study is to evaluate the effect of hypobranchial gland protein extracts (HGPEs) of Hexaplex trunculus on the viability, cell adhesion, and migration of human U87 glioblastoma cells and the HeLa cell line obtained from epithelial cervical carcinoma cells. Analysis of the HGPE on polyacrylamide gel (12%) shows a variety of proteins whose molecular weights vary between 12 and 1OO kDa. Chromatographic analysis shows 16 peaks obtained at various retention times. Cytotoxic effect was observed after 24 hours of incubation at the concentrations 20, 40, and 60 μg/ml in a dose-dependent manner...
October 2017: Nutrition and Cancer
https://www.readbyqxmd.com/read/29023168/development-and-characterization-of-cationic-solid-lipid-nanoparticles-for-co-delivery-of-pemetrexed-and-mir-21-antisense-oligonucleotide-to-glioblastoma-cells
#10
Berrin Küçüktürkmen, Asuman Bozkır
The practical use of solid lipid nanoparticles (SLNs) in research has been highlighted in the literature, but few reports have combined SLNs with miRNA-based therapy and chemotherapy. We aimed to prepare cationic SLNs (cSLNs) to load anti-miR-21 oligonucleotide and pemetrexed for glioblastoma therapy in vitro. cSLNs were employed to encapsulate both pemetrexed and anti-miR-21 by a high-pressure homogenization method, and then the properties of cSLNs were characterized. We studied cellular uptake and cytotoxicity properties of cSLNs in U87MG cells...
February 2018: Drug Development and Industrial Pharmacy
https://www.readbyqxmd.com/read/29020502/persistence-of-dna-adducts-hypermutation-and-acquisition-of-cellular-resistance-to-alkylating-agents-in-glioblastoma
#11
R J Head, M F Fay, L Cosgrove, K Y C Fung, D Rundle-Thiele, J H Martin
Glioblastoma is a lethal form of brain tumour usually treated by surgical resection followed by radiotherapy and an alkylating chemotherapeutic agent. Key to the success of this multimodal approach is maintaining apoptotic sensitivity of tumour cells to the alkylating agent. This initial treatment likely establishes conditions contributing to development of drug resistance as alkylating agents form the O6 -methylguanine adduct. This activates the mismatch repair (MMR) process inducing apoptosis and mutagenesis...
December 2, 2017: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/28895245/genetic-evolution-of-glioblastoma-stem-like-cells-from-primary-to-recurrent-tumor
#12
Francesca Orzan, Francesca De Bacco, Giovanni Crisafulli, Serena Pellegatta, Benedetta Mussolin, Giulia Siravegna, Antonio D'Ambrosio, Paolo M Comoglio, Gaetano Finocchiaro, Carla Boccaccio
Glioblastoma (GBM) is a lethal tumor that displays remarkable genetic heterogeneity. It is also known that GBM contains a cell hierarchy driven by GBM stem-like cells (GSCs), responsible for tumor generation, therapeutic resistance, and relapse. An important and still open issue is whether phylogenetically related GSCs can be found in matched primary and recurrent GBMs, and reflect tumor genetic evolution under therapeutic pressure. To address this, we analyzed the mutational profile of GSCs isolated from either human primary GBMs (primary GSCs) or their matched tumors recurring after surgery and chemoradiotherapy (recurrent GSCs)...
November 2017: Stem Cells
https://www.readbyqxmd.com/read/28753575/glioblastoma-and-glioblastoma-stem-cells-are-dependent-on-functional-mth1
#13
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/28717226/safe-brain-tumor-resection-does-not-depend-on-surgery-alone-role-of-hemodynamics
#14
Stefanie Bette, Benedikt Wiestler, Felicitas Wiedenmann, Johannes Kaesmacher, Martin Bretschneider, Melanie Barz, Thomas Huber, Yu-Mi Ryang, Eberhard Kochs, Claus Zimmer, Bernhard Meyer, Tobias Boeckh-Behrens, Jan S Kirschke, Jens Gempt
Aim of this study was to determine if perioperative hemodynamics have an impact on perioperative infarct volume and patients' prognosis. 201 cases with surgery for a newly diagnosed or recurrent glioblastoma were retrospectively analyzed. Clinical data and perioperative hemodynamic parameters, blood tests and time of surgery were recorded. Postoperative infarct volume was quantitatively assessed by semiautomatic segmentation. Mean diastolic blood pressure (dBP) during surgery (rho -0.239, 95% CI -0.11 - -0...
July 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28706148/expression-differences-of-programmed-death-ligand-1-in-de-novo-and-recurrent-glioblastoma-multiforme
#15
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/28696296/multiplexed-rnai-therapy-against-brain-tumor-initiating-cells-via-lipopolymeric-nanoparticle-infusion-delays-glioblastoma-progression
#16
Dou Yu, Omar F Khan, Mario L Suvà, Biqin Dong, Wojciech K Panek, Ting Xiao, Meijing Wu, Yu Han, Atique U Ahmed, Irina V Balyasnikova, Hao F Zhang, Cheng Sun, Robert Langer, Daniel G Anderson, Maciej S Lesniak
Brain tumor-initiating cells (BTICs) have been identified as key contributors to therapy resistance, recurrence, and progression of diffuse gliomas, particularly glioblastoma (GBM). BTICs are elusive therapeutic targets that reside across the blood-brain barrier, underscoring the urgent need to develop novel therapeutic strategies. Additionally, intratumoral heterogeneity and adaptations to therapeutic pressure by BTICs impede the discovery of effective anti-BTIC therapies and limit the efficacy of individual gene targeting...
July 25, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28685138/immunophenotypic-signature-of-primary-glioblastoma-multiforme-a-case-of-extended-progression-free-survival
#17
Puneet Gandhi, Richa Khare, Nitin Garg, Sandeep Sorte
Glioblastoma-multiforme (GBM), the most aggressive glial tumor, has a worldwide age-adjusted incidence ranging from 0.59-3.69/100000 persons. Despite current multimodal-treatment approach, median-survival time and progression-free survival (PFS) remains short. Glioblastomas display a variety of molecular alterations, which necessitates determining which of these have a prognostic significance. This is a case of a 45-year-old patient who presented with progressive slurring of speech and features of raised intracranial pressure...
June 16, 2017: World Journal of Clinical Cases
https://www.readbyqxmd.com/read/28666727/liposomal-temozolomide-drug-delivery-using-convection-enhanced-delivery
#18
COMPARATIVE STUDY
Mirjam M Nordling-David, Roni Yaffe, David Guez, Hadar Meirow, David Last, Etty Grad, Sharona Salomon, Shirley Sharabi, Yael Levi-Kalisman, Gershon Golomb, Yael Mardor
Even though some progress in diagnosis and treatment has been made over the years, there is still no definitive treatment available for Glioblastoma multiforme (GBM). Convection-enhanced delivery (CED), a continuous infusion-mediated pressure gradient via intracranial catheters, studied in clinical trials, enables in situ drug concentrations several orders of magnitude greater than those achieved by systemic administration. We hypothesized that the currently limited efficacy of CED could be enhanced by a liposomal formulation, thus achieving enhanced drug localization to the tumor site with minimal toxicity...
September 10, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28663722/bacoside-a-induces-tumor-cell-death-in-human-glioblastoma-cell-lines-through-catastrophic-macropinocytosis
#19
Sebastian John, K C Sivakumar, Rashmi Mishra
Glioblastoma multiforme (GBM) is a highly aggressive type of brain tumor with an extremely poor prognosis. Recent evidences have shown that the "biomechanical imbalances" induced in GBM patient-derived glioblastoma cells (GC) and in vivo via the administration of synthetic small molecules, may effectively inhibit disease progression and prolong survival of GBM animal models. This novel concept associated with de novo anti-GBM drug development has however suffered obstacles in adequate clinical utility due to the appearance of unrelated toxicity in the prolonged therapeutic windows...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28542439/host-mediated-inflammatory-influence-on-glioblastoma-multiforme-recurrence-following-high-dose-ionizing-radiation
#20
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
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