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Bevacizumab glioblastoma

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https://www.readbyqxmd.com/read/28218903/macrophage-migration-inhibitory-factor-downregulation-a-novel-mechanism-of-resistance-to-anti-angiogenic-therapy
#1
B A Castro, P Flanigan, A Jahangiri, D Hoffman, W Chen, R Kuang, M De Lay, G Yagnik, J R Wagner, S Mascharak, M Sidorov, S Shrivastav, G Kohanbash, H Okada, M K Aghi
Anti-angiogenic therapies for cancer such as VEGF neutralizing antibody bevacizumab have limited durability. While mechanisms of resistance remain undefined, it is likely that acquired resistance to anti-angiogenic therapy will involve alterations of the tumor microenvironment. We confirmed increased tumor-associated macrophages in bevacizumab-resistant glioblastoma patient specimens and two novel glioblastoma xenograft models of bevacizumab resistance. Microarray analysis suggested downregulated macrophage migration inhibitory factor (MIF) to be the most pertinent mediator of increased macrophages...
February 20, 2017: Oncogene
https://www.readbyqxmd.com/read/28204639/comparison-of-2d-rano-and-volumetric-methods-for-assessment-of-recurrent-glioblastoma-treated-with-bevacizumab-a-report-from-the-belob-trial
#2
Renske Gahrmann, Martin van den Bent, Bronno van der Holt, René Michel Vernhout, Walter Taal, Maaike Vos, Jan Cees de Groot, Laurens Victor Beerepoot, Jan Buter, Zwenneke Hendrieke Flach, Monique Hanse, Bas Jasperse, Marion Smits
No abstract text is available yet for this article.
February 13, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/28202289/rolipram-potentiates-bevacizumab-induced-cell-death-in-human-glioblastoma-stem-like-cells
#3
Sara Ramezani, Nasim Vousooghi, Fatemeh Ramezani Kapourchali, Mahmoudreza Hadjighasem, Parisa Hayat, Naser Amini, Mohammad Taghi Joghataei
AIMS: Glioblastoma cancer stem-like cells (GCSCs) promote themselves proliferation by secreting the vascular endothelial growth factor A (VEGFA) in an autocrine manner, positively regulated by phosphodiesterase IV (PDE4). In the current study, we investigated the putative cytotoxic effect of bevacizumab, a VEGFA blocker, alone and in combination with a specific inhibitor of PDE4 called rolipram on GCSCs isolated from human surgical tumor specimen with a focus on PI3K/AKT pathway. MAIN METHODS: CD133+/CD15+ GCSCs were characterized by flow cytometry and expanded in a serum-free primary culture system...
February 12, 2017: Life Sciences
https://www.readbyqxmd.com/read/28176936/add-on-bevacizumab-can-prevent-early-clinical-deterioration-and-prolong-survival-in-newly-diagnosed-partially-resected-glioblastoma-patients-with-a-poor-performance-status
#4
Nobuhiro Hata, Koji Yoshimoto, Ryusuke Hatae, Daisuke Kuga, Yojiro Akagi, Yuhei Sangatsuda, Satoshi O Suzuki, Tadahisa Shono, Masahiro Mizoguchi, Koji Iihara
PURPOSE: The AVAglio trial established the beneficial effect of add-on bevacizumab (BEV) for the treatment of newly diagnosed glioblastomas (nd-GBMs) that led to the approval of BEV for the treatment of these patients in Japan. However, the rationality of using BEV as a first-line treatment for nd-GBMs remains controversial. The purpose of this study was to analyze the outcomes of a case series of nd-GBM patients. PATIENTS AND METHODS: The outcomes of 69 nd-GBM patients treated after 2006 were retrospectively analyzed...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28165649/intracellular-ph-measured-by-31-p-mr-spectroscopy-might-predict-site-of-progression-in-recurrent-glioblastoma-under-antiangiogenic-therapy
#5
Katharina J Wenger, Elke Hattingen, Kea Franz, Joachim P Steinbach, Oliver Bähr, Ulrich Pilatus
PURPOSE: In solid tumors, changes in the expression/activity of plasma membrane ion transporters facilitate proton efflux and enable tumor cells to maintain a higher intracellular pH (pHi ), while the microenvironment (pHe ) is commonly more acidic. This supports various tumor-promoting mechanisms. We propose that these changes in pH take place before a magnetic resonance imaging (MRI)-detectable brain tumor recurrence occurs. MATERIALS AND METHODS: We enrolled 66 patients with recurrent glioblastoma, treated with bevacizumab...
February 6, 2017: Journal of Magnetic Resonance Imaging: JMRI
https://www.readbyqxmd.com/read/28153956/influence-of-bevacizumab-on-blood-brain-barrier-permeability-and-o-2-18f-fluoroethyl-l-tyrosine-uptake-in-rat-gliomas
#6
Carina Stegmayr, Dennis Oliveira, Nicole Niemietz, Antje Willuweit, Philipp Lohmann, Norbert Galldiks, N Jon Shah, Johannes Ermert, Karl-Josef Langen
PURPOSE: Restoration of the blood-brain barrier (BBB) following antiangiogenic therapy of gliomas using Bevacizumab may result in a decrease of contrast enhancement in magnet resonance imaging (MRI) despite tumor progression. This so called pseudoresponse is difficult to differentiate from true tumor response with conventional MRI. First patient studies have indicated that positron emission tomography (PET) using O-(2-(18)F-fluoroethyl)-L-tyrosine ((18)F-FET) may be helpful to solve this diagnostic problem...
February 2, 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/28138554/glut3-upregulation-promotes-metabolic-reprogramming-associated-with-antiangiogenic-therapy-resistance
#7
Ruby Kuang, Arman Jahangiri, Smita Mascharak, Alan Nguyen, Ankush Chandra, Patrick M Flanigan, Garima Yagnik, Jeffrey R Wagner, Michael De Lay, Diego Carrera, Brandyn A Castro, Josie Hayes, Maxim Sidorov, Jose Luiz Izquierdo Garcia, Pia Eriksson, Sabrina Ronen, Joanna Phillips, Annette Molinaro, Suneil Koliwad, Manish K Aghi
Clinical trials revealed limited response duration of glioblastomas to VEGF-neutralizing antibody bevacizumab. Thriving in the devascularized microenvironment occurring after antiangiogenic therapy requires tumor cell adaptation to decreased glucose, with 50% less glucose identified in bevacizumab-treated xenografts. Compared with bevacizumab-responsive xenograft cells, resistant cells exhibited increased glucose uptake, glycolysis, (13)C NMR pyruvate to lactate conversion, and survival in low glucose. Glucose transporter 3 (GLUT3) was upregulated in bevacizumab-resistant versus sensitive xenografts and patient specimens in a HIF-1α-dependent manner...
January 26, 2017: JCI Insight
https://www.readbyqxmd.com/read/28134851/barriers-to-the-access-of-bevacizumab-in-patients-with-solid-tumors-and-the-potential-impact-of-biosimilars-a-physician-survey
#8
Bradley J Monk, Philip E Lammers, Thomas Cartwright, Ira Jacobs
Access to bevacizumab, an important component of oncology treatment regimens, may be limited. This survey of oncologists in the US (n = 150), Europe (n = 230), and emerging markets (EM: Brazil, Mexico, and Turkey; n = 130) examined use of and barriers to accessing bevacizumab as treatment of advanced solid tumors. We also assessed the likelihood that physicians would prescribe a bevacizumab biosimilar, if available. Bevacizumab was frequently used as early-line therapy in metastatic colorectal cancer, metastatic non-squamous non-small-cell lung cancer, and metastatic ovarian cancer (all markets), and as a second-line therapy in glioblastoma multiforme (US, EM)...
January 28, 2017: Pharmaceuticals
https://www.readbyqxmd.com/read/28123740/efficacy-of-bevacizumab-therapy-for-unresectable-malignant-glioma-a-retrospective-analysis
#9
Hajime Yonezawa, Hirofumi Hirano, Hiroyuki Uchida, Mika Habu, Ryosuke Hanaya, Tatsuki Oyoshi, Yuko Sadamura, Tomoko Hanada, Hiroshi Tokimura, Fm Moinuddin, Kazunori Arita
Bevacizumab (BEV), an inhibitor of vascular endothelial growth factor A, has been used for primary and recurrent malignant gliomas in Japan since June, 2013. Previous randomized controlled studies demonstrated that BEV prolonged the progression-free survival, but not the overall survival (OS) of patients with newly diagnosed glioblastoma. The aim of the present study was to elucidate the effect of BEV on the OS of patients with unresectable malignant gliomas. Of the 440 cases of malignant glioma initially treated in our institute between 2000 and 2015, 88 were not suitable for maximal resection due to patient age, physical condition, tumor location and extent, or the patient's wishes...
January 2017: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/28074323/changes-in-cerebral-metabolism-during-ketogenic-diet-in-patients-with-primary-brain-tumors-1-h-mrs-study
#10
Moran Artzi, Gilad Liberman, Nachum Vaisman, Felix Bokstein, Faina Vitinshtein, Orna Aizenstein, Dafna Ben Bashat
Normal brain cells depend on glucose metabolism, yet they have the flexibility to switch to the usage of ketone bodies during caloric restriction. In contrast, tumor cells lack genomic and metabolic flexibility and are largely dependent on glucose. Ketogenic-diet (KD) was suggested as a therapeutic option for malignant brain cancer. This study aimed to detect metabolic brain changes in patients with malignant brain gliomas on KD using proton magnetic-resonance-spectroscopy ((1)H-MRS). Fifty MR scans were performed longitudinally in nine patients: four patients with recurrent glioblastoma (GB) treated with KD in addition to bevacizumab; one patient with gliomatosis-cerebri treated with KD only; and four patients with recurrent GB who did not receive KD...
January 10, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28057017/the-brain-penetrating-cxcr4-antagonist-prx177561-increases-the-antitumor-effects-of-bevacizumab-and-sunitinib-in-preclinical-models-of-human-glioblastoma
#11
Giovanni Luca Gravina, Andrea Mancini, Francesco Marampon, Alessandro Colapietro, Simona Delle Monache, Roberta Sferra, Flora Vitale, Peter J Richardson, Lee Patient, Stephen Burbidge, Claudio Festuccia
BACKGROUND: Glioblastoma recurrence after treatment with the anti-vascular endothelial growth factor (VEGF) antibody bevacizumab is characterized by a highly infiltrative and malignant behavior that renders surgical excision and chemotherapy ineffective. It has been demonstrated that anti-VEGF/VEGFR therapies control the invasive phenotype and that relapse occurs through the increased activity of CXCR4. We therefore hypothesized that combining bevacizumab or sunitinib with the novel CXCR4 antagonist, PRX177561, would have superior antitumor activity...
January 5, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28048647/tu-d-207b-07-radiomic-response-assessment-for-recurrent-glioblastoma-treated-with-bevacizumab-in-the-brain-trial
#12
P Grossmann, V Narayan, R Huang, H Aerts
PURPOSE: To develop radiomic biomarkers for non-invasive response assessment of Bevacizumab (Avastin; Genentech) treatment in recurrent glioblastoma multiforme (GBM). METHODS: We analyzed prospectively acquired data from the BRAIN trial. For 167 patients, we extracted 71 radiomic features each from normalized post-contrast T1-weighted and fluid attenuation inversion recovery (FLAIR) sequences at baseline (pretreatment), and at follow-ups of six and twelve weeks (post-treatment), respectively, where available...
June 2016: Medical Physics
https://www.readbyqxmd.com/read/28046101/single-cell-mathematical-model-successfully-replicates-key-features-of-gbm-go-or-grow-is-not-necessary
#13
Elizabeth Scribner, Hassan M Fathallah-Shaykh
Glioblastoma (GBM) is a malignant brain tumor that continues to be associated with neurological morbidity and poor survival times. Brain invasion is a fundamental property of malignant glioma cells. The Go-or-Grow (GoG) phenotype proposes that cancer cell motility and proliferation are mutually exclusive. Here, we construct and apply a single glioma cell mathematical model that includes motility and angiogenesis and lacks the GoG phenotype. Simulations replicate key features of GBM including its multilayer structure (i...
2017: PloS One
https://www.readbyqxmd.com/read/28011470/advances-in-experimental-targeted-therapy-and-immunotherapy-for-patients-with-glioblastoma-multiforme
#14
REVIEW
Jiri Polivka, Jiri Polivka, Lubos Holubec, Tereza Kubikova, Vladimir Priban, Ondrej Hes, Kristyna Pivovarcikova, Inka Treskova
Glioblastoma multiforme (GBM) represents the most malignant primary brain tumor in adults with generally dismal prognosis, early clinical deterioration and high mortality. GBM is extremely invasive, characterized by intense and aberrant vascularization and high resistance to multimodal treatment. Standard therapy (surgery, radiotherapy and chemotherapy with temozolomide) has very limited effectiveness, with median overall survival of patients no longer than 15 months. Progress in genetics and epigenetics of GBM over the past decade has revealed various aberrations in cellular signaling pathways, the tumor microenvironment, and pathological angiogenesis...
2017: Anticancer Research
https://www.readbyqxmd.com/read/28007759/magnetic-resonance-perfusion-image-features-uncover-an-angiogenic-subgroup-of-glioblastoma-patients-with-poor-survival-and-better-response-to-antiangiogenic-treatment
#15
Tiffany T Liu, Achal S Achrol, Lex A Mitchell, Scott A Rodriguez, Abdullah Feroze, Christine Kim, Navjot Chaudhary, Olivier Gevaert, Josh M Stuart, Griffith R Harsh, Steven D Chang, Daniel L Rubin
BACKGROUND: In previous clinical trials, antiangiogenic therapies such as bevacizumab did not show efficacy in patients with newly diagnosed glioblastoma (GBM). This may be a result of the heterogeneity of GBM, which has a variety of imaging-based phenotypes and gene expression patterns. In this study, we sought to identify a phenotypic subtype of GBM patients who have distinct tumor-image features and molecular activities and who may benefit from antiangiogenic therapies. METHODS: Quantitative image features characterizing subregions of tumors and the whole tumor were extracted from preoperative and pretherapy perfusion magnetic resonance (MR) images of 117 GBM patients in 2 independent cohorts...
December 22, 2016: Neuro-oncology
https://www.readbyqxmd.com/read/28005980/the-prognosis-of-anti-angiogenesis-treatments-combined-with-standard-therapy-for-newly-diagnosed-glioblastoma-a-meta-analysis-of-randomized-controlled-trials
#16
Yuping Li, Mengzhuo Hou, Guangyu Lu, Natalia Ciccone, Xingdong Wang, Hengzhu Zhang
BACKGROUND AND PURPOSE: Although bevacizumab (BV) has been approved as second-line therapy for recurrent glioblastoma (GB), the efficacy and safety of BV for patients with newly diagnosed GB remain unclear. METHODOLOGY/PRINCIPAL FINDINGS: We systematically searched electronic databases (PubMed, EMBASE, OVID, etc.) to identify related studies published from January 1966 and August 2016. Eight randomized controlled trials including a total of 2,185 patients with GB were included...
2016: PloS One
https://www.readbyqxmd.com/read/28001091/treatment-options-for-recurrent-high-grade-gliomas
#17
Harjus S Birk, Seunggu J Han, Nicholas A Butowski
High-grade gliomas are aggressive brain tumors encompassing Grade III and IV classifications. Of these, glioblastoma (GB) is the most malignant with a high rate of recurrence after initial resection. Although standard treatment does exist for newly diagnosed GBs, therapeutic strategies for recurrent GB are less solidified. However, mounting evidence describes the role of re-resection, bevacizumab, chemotherapy, targeted molecular therapies, immunotherapeutic approaches and radiotherapy in recurrent GB management...
January 2017: CNS Oncology
https://www.readbyqxmd.com/read/27942839/immune-modulation-associated-with-vascular-endothelial-growth-factor-vegf-blockade-in-patients-with-glioblastoma
#18
Alissa A Thomas, Jan L Fisher, Thomas H Hampton, Brock C Christensen, Gregory J Tsongalis, Gilbert J Rahme, Chery A Whipple, Sandra E Steel, Melissa C Davis, Arti B Gaur, Lionel D Lewis, Marc S Ernstoff, Camilo E Fadul
BACKGROUND: Vascular endothelial growth factor (VEGF), in addition to being pro-angiogenic, is an immunomodulatory cytokine systemically and in the tumor microenvironment. We previously reported the immunomodulatory effects of radiation and temozolomide (TMZ) in newly diagnosed glioblastoma. This study aimed to assess changes in peripheral blood mononuclear cell (PBMC) populations, plasma cytokines, and growth factor concentrations following treatment with radiation, TMZ, and bevacizumab (BEV)...
December 9, 2016: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/27940247/sdf-1-blockade-enhances-anti-vegf-therapy-of-glioblastoma-and-can-be-monitored-by-mri
#19
Lei Deng, Jason H Stafford, Shie-Chau Liu, Sophia B Chernikova, Milton Merchant, Lawrence Recht, J Martin Brown
Despite the approval of antiangiogenic therapy for glioblastoma multiforme (GBM) patients, survival benefits are still limited. One of the resistance mechanisms for antiangiogenic therapy is the induction of hypoxia and subsequent recruitment of macrophages by stromal-derived factor (SDF)-1α (CXCL-12). In this study, we tested whether olaptesed pegol (OLA-PEG, NOX-A12), a novel SDF-1α inhibitor, could reverse the recruitment of macrophages and potentiate the antitumor effect of anti-vascular endothelial growth factor (VEGF) therapy...
December 7, 2016: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/27918718/randomized-double-blind-placebo-controlled-multicenter-phase-ii-study-of-onartuzumab-plus-bevacizumab-versus-placebo-plus-bevacizumab-in-patients-with-recurrent-glioblastoma-efficacy-safety-and-hepatocyte-growth-factor-and-o-6-methylguanine-dna-methyltransferase
#20
Timothy Cloughesy, Gaetano Finocchiaro, Cristóbal Belda-Iniesta, Lawrence Recht, Alba A Brandes, Estela Pineda, Tom Mikkelsen, Olivier L Chinot, Carmen Balana, David R Macdonald, Manfred Westphal, Kirsten Hopkins, Michael Weller, Carlos Bais, Thomas Sandmann, Jean-Marie Bruey, Hartmut Koeppen, Bo Liu, Wendy Verret, See-Chun Phan, David S Shames
Purpose Bevacizumab regimens are approved for the treatment of recurrent glioblastoma in many countries. Aberrant mesenchymal-epithelial transition factor (MET) expression has been reported in glioblastoma and may contribute to bevacizumab resistance. The phase II study GO27819 investigated the monovalent MET inhibitor onartuzumab plus bevacizumab (Ona + Bev) versus placebo plus bevacizumab (Pla + Bev) in recurrent glioblastoma. Methods At first recurrence after chemoradiation, bevacizumab-naïve patients with glioblastoma were randomly assigned 1:1 to receive Ona (15 mg/kg, once every 3 weeks) + Bev (15 mg/kg, once every 3 weeks) or Pla + Bev until disease progression...
January 20, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
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