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Christine Wang, Xinming Tong, Xinyi Jiang, Fan Yang
Glioblastoma (GBM) is the most common and aggressive form of primary brain tumor with median survival of 12 months. To improve clinical outcomes, it is critical to develop in vitro models that support GBM proliferation and invasion for deciphering tumor progression and screening drug candidates. A key hallmark of GBM cells is their extreme invasiveness, a process mediated by matrix metalloproteinase (MMP)-mediated degradation of the extracellular matrix. We recently reported the development of a MMP-degradable, poly(ethylene-glycol)-based hydrogel platform for culturing GBM cells...
October 22, 2016: Journal of Biomedical Materials Research. Part A
Mark R Gilbert, Stephanie L Pugh, Ken Aldape, A Gregory Sorensen, Tom Mikkelsen, Marta Penas-Prado, Felix Bokstein, Young Kwok, R Jeffrey Lee, Minesh Mehta
Angiogenesis, a hallmark of glioblastoma, can potentially be targeted by inhibiting the VEGF pathway using bevacizumab, a humanized monoclonal antibody against VEGF-A. This study was designed to determine the efficacy and safety of these regimens in the cooperative group setting. Eligibility included age ≥18, recurrent or progressive GBM after standard chemoradiation. Treatment was intravenous bevacizumab 10 mg/kg and either irinotecan (CPT) 125 mg/m(2) every 2 weeks or temozolomide (TMZ) 75-100 mg/m(2) day 1-21 of 28 day cycle...
October 21, 2016: Journal of Neuro-oncology
Duthika M Mallawaaratchy, Susannah Hallal, Ben Russell, Linda Ly, Saeideh Ebrahimkhani, Heng Wei, Richard I Christopherson, Michael E Buckland, Kimberley L Kaufman
Extracellular vesicles (EVs) play key roles in glioblastoma (GBM) biology and represent novel sources of biomarkers that are detectable in the peripheral circulation. Despite this notionally non-invasive approach to assess GBM tumours in situ, a comprehensive GBM EV protein signature has not been described. Here, EVs secreted by six GBM cell lines were isolated and analysed by quantitative high-resolution mass spectrometry. Overall, 844 proteins were identified in the GBM EV proteome, of which 145 proteins were common to EVs secreted by all cell lines examined; included in the curated EV compendium (Vesiclepedia_559; http://microvesicles...
October 21, 2016: Journal of Neuro-oncology
Qiyong Jiang, Yimin Liu, Shijuan Zhang, Naikun Li, Gaoling Sun
MiRNAs are emerging as important epigenetic modulators of multiple target genes, leading to abnormal cellular signaling involving cellular proliferation in cancers. Aberrant miRNA expression has been observed in human glioblastoma (GBM). The present study was to evaluate the expression and molecular mechanisms of COX-2 and miR-26b in human GBM tissues and GBM cell lines T98G, U87 and U251. In the present study, we found that expression of miR-26b was markedly downregulated in GBM cell lines and human GBM tissues, compared to matched non-tumor associated tissues...
October 17, 2016: Oncotarget
S Sengupta, G Mao, Z S Gokaslan, P Sampath
Glioblastoma (GBM) is by far the most common and the most aggressive of all the primary brain malignancies. No curative therapy exists, and median life expectancy hovers at around 1 year after diagnosis, with a minute fraction surviving beyond 5 years. The difficulty in treating GBM lies in the cancer's protected niche within the blood-brain barrier and the heterogeneity of the cancer cells, which possess varying degrees of susceptibility to various common modalities of treatment. Over time, it is the tumor heterogeneity of GBM and the ability of the cancer stem cells to evolve in response treatment that renders the cancer refractory to conventional treatment...
October 21, 2016: Cancer Gene Therapy
Mikkel Staberg, Signe Regner Michaelsen, Rikke Darling Rasmussen, Mette Villingshøj, Hans Skovgaard Poulsen, Petra Hamerlik
PURPOSE: Glioblastoma (GBM) ranks among the deadliest solid cancers worldwide and its prognosis has remained dismal, despite the use of aggressive chemo-irradiation treatment regimens. Limited drug delivery into the brain parenchyma and frequent resistance to currently available therapies are problems that call for a prompt development of novel therapeutic strategies. While only displaying modest efficacies as mono-therapy in pre-clinical settings, histone deacetylase inhibitors (HDACi) have shown promising sensitizing effects to a number of cytotoxic agents...
October 20, 2016: Cellular Oncology (Dordrecht)
Gina Lee, Brenda Auffinger, Donna Guo, Tanwir Hasan, Marc Deheeger, Alex L Tobias, Jeong Yeon Kim, Fatemeh Atashi, Lingjiao Zhang, Maciej S Lesniak, James C David, Atique U Ahmed
Increasing evidence exposes a subpopulation of cancer cells, known as cancer stem cells (CSCs), to be critical for the progression of several human malignancies, including glioblastoma multiforme (GBM). CSCs are highly tumorigenic, capable of self-renewal, and resistant to conventional therapies, and thus considered to be one of the key contributors to disease recurrence. In order to elucidate the poorly understood evolutionary path of tumor recurrence and the role of CSCs in this process, we developed patient-derived xenograft GBM recurrent models induced by anti-glioma chemotherapy, temozolomide (TMZ)...
October 7, 2016: Molecular Cancer Therapeutics
J P Cata, K B Hagan, S D O Bhavsar, R Arunkumar, R Grasu, A Dang, R Carlson, B Arnold, Y Potylchansky, I Lipski, T McHugh, F Jimenez, A T Nguyen, L Feng, T F Rahlfs
BACKGROUND: Several studies have examined the impact of anesthetics on cancer recurrence. Isoflurane but not desflurane has protumoral effects. We hypothesize the use of isoflurane but not desflurane during surgery for primary GBM is an independent predictor of disease progression and mortality. METHODS: 378 adult patients were included in the study. The progression free survival (PFS) and overall survival (OS) rates at 1 and 5years were compared in patients who had either desflurane or isoflurane alone or in combination with propofol infusion...
October 17, 2016: Journal of Clinical Neuroscience: Official Journal of the Neurosurgical Society of Australasia
Uday B Maachani, Uma Shankavaram, Tamalee Kramp, Philip J Tofilon, Kevin Camphausen, Anita T Tandle
Glioblastoma multiforme (GBM) continues to be the most frequently diagnosed and lethal primary brain tumor. Adjuvant chemo-radiotherapy remains the standard of care following surgical resection. In this study, using reverse phase protein arrays (RPPAs), we assessed the biological effects of radiation on signaling pathways to identify potential radiosensitizing molecular targets. We identified subsets of proteins with clearly concordant/discordant behavior between irradiated and non-irradiated GBM cells in vitro and in vivo...
October 14, 2016: Oncotarget
Hailong Li, Jiye Li, Gang Cheng, Jianning Zhang, Xuezhen Li
PURPOSE: This study aimed to investigate the potential association between IDH mutation and O(6)-methyl-guanine methyl transferase (MGMT) gene promoter methylation and pseudoprogression disease (psPD) in glioblastoma multiforme (GBM) patients after concurrent temozolomide (TMZ)-based chemoradiotherapy. METHODS: A total of 157 GBM patients who received concurrent TMZ-based chemoradiotherapy were included in this retrospective study. The association between psPD and a number of demographic and genetic factors, including IDH mutation and MGMT promoter methylation, were analyzed based on logistic regression, Cox regression, and multivariate analysis...
October 12, 2016: Clinical Neurology and Neurosurgery
Pelin Erkoc, Ahmet Cingöz, Tugba Bagci Onder, Seda Kizilel
Overcoming drug resistance is a major challenge for cancer therapy. Tumor necrosis factor α-related apoptosis-inducing ligand (TRAIL) is a potent therapeutic as an activator of apoptosis, particularly in tumor but not in healthy cells. However, its efficacy is limited by the resistance of tumor cell populations to the therapeutic substance. Here, we have addressed this limitation through the development of a controlled release system, matrix-metalloproteinase (MMP)-sensitive and arg-gly-asp-ser (RGDS) peptide functionalized poly (ethylene-glycol) (PEG) particles which are synthesized via visible-light-induced water-in-water emulsion polymerization...
October 20, 2016: Macromolecular Bioscience
Zhangjing Yang, Piaopiao Feng, Tian Wen, Minghua Wan, Xunning Hong
Differentiation of glioblastoma multiformes (GBMs) and lymphomas using multi-sequence magnetic resonance imaging (MRI) is an important task that is valuable for treatment planning. However, this task is a challenge because GBMs and lymphomas may have a similar appearance in MRI images. This similarity may lead to misclassification and could affect the treatment results. In this paper, we propose a semi-automatic method based on multi-sequence MRI to differentiate these two types of brain tumors. Our method consists of three steps: 1) the key slice is selected from 3D MRIs and region of interests (ROIs) are drawn around the tumor region; 2) different features are extracted based on prior clinical knowledge and validated using a t-test; and 3) features that are helpful for classification are used to build an original feature vector and a support vector machine is applied to perform classification...
October 18, 2016: CNS & Neurological Disorders Drug Targets
Kara W Moyes, Nicole Ap Lieberman, Shannon A Kreuser, Harrison Chinn, Conrad Winter, Gail Deutsch, Virginia Hoglund, Reid Watson, Courtney A Crane
In spite of their successes against hematologic malignancies, immunotherapeutic interventions for the treatment of patients with glioblastoma (GBM) have thus far been unsuccessful. This is in part due to the presence of a tumor microenvironment that fosters neoplastic growth and protects the tumor from destruction by the immune system. We have developed a novel genetically engineered macrophage-based platform with the potential to minimize the effects of the suppressive tumor microenvironment and improve innate and adaptive anti-tumor immune responses...
October 19, 2016: Human Gene Therapy
Liang Leng, Xiaojun Zhong, Guan Sun, Wen Qiu, Lei Shi
Temozolomide (TMZ) is widely used in the treatment of glioblastoma multiforme (GBM) as it can effectively inhibit the growth of GBM for some months; however, this cancer type is still incurable. The existence of glioma stem cells (GSCs) is thought to be responsible for the invariable recurrence of GBM after treatment, but GSCs are insensitive to TMZ. Our recent research showed that demethoxycurcumin (DMC), a component of curcumin, was superior to TMZ in its ability to inhibit proliferation and induce apoptosis of GSCs in vitro...
October 18, 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
Chenran Zhang, Wei Meng, Jiajia Wang, Yicheng Lu, Guohan Hu, Liuhua Hu, Jie Ma
Retinoblastoma protein-interacting zinc-finger gene 1 (RIZ1), a strong tumor suppressor, is silenced in many human cancers. Our previous studies showed that RIZ1 expression was negatively correlated with the grade of glioma and was a key predictor of patient survival. Therefore, RIZ1 could be a potential tumor suppressor during glioma pathogenesis, although the mechanism underlying RIZ1 gene inactivation in gliomas is unknown. We investigated the methylation status of the RIZ1 promoter in human glioma tissues and four glioblastoma (GBM) cell lines, and verified the effect of the methyltransferase inhibitor 5-aza-2-deoxycytidine (5-aza-CdR) on RIZ1 transcription and cell proliferation...
October 18, 2016: Cellular and Molecular Neurobiology
Sanne Duinkerken, Yvette van Kooyk, Juan J Garcia-Vallejo
Glioblastoma multiforme (GBM) is the most aggressive brain tumor and median survival time with current therapies is only 14.6 mo. Although multiple immunotherapeutic strategies are being explored, efficacy remains poor. In order to improve immunotherapy for GBM, we propose to combine currently used endogenous with human cytomegalovirus (HCMV) specific antigens expressed on cancer cells.
2016: Oncoimmunology
Nathan B Roberts, Aniket S Wadajkar, Jeffrey A Winkles, Eduardo Davila, Anthony J Kim, Graeme F Woodworth
Glioblastoma (GBM) is a fatal brain cancer for which new treatment options are sorely needed. Platinum-based drugs have been investigated extensively for GBM treatment but few have shown significant efficacy without major central nervous system (CNS) and systemic toxicities. The relative success of platinum drugs for treatment of non-CNS cancers indicates great therapeutic potential when effectively delivered to the tumor region(s). New insights into the broad anticancer effects of platinum drugs, particularly immunomodulatory effects, and innovative delivery strategies that can maximize these multi-modal effects and minimize toxicities may promote the re-purposing of this chemotherapeutic drug class for GBM treatment...
2016: Oncoimmunology
Lin Zhang, Gan Wang, Shiwen Chen, Jun Ding, Shiming Ju, Heli Cao, Hengli Tian
BACKGROUND: Glioblastoma (GBM) is the most malignant nervous system tumor with an almost 100 % recurrence rate. Thymopoietin (TMPO) has been demonstrated to be upregulated in various tumors, including lung cancer, breast cancer, and so on, but its role in GBM has not been reported. This study was aimed to determine the role of TMPO in GBM. METHODS: Publicly available Oncomine dataset analysis was used to explore the expression level of TMPO in GBM specimens. Then the expression of TMPO was knocked down in GBM cells using lentiviral system, and the knockdown efficacy was further validated by real-time quantitative PCR and western blot analysis...
October 19, 2016: World Journal of Surgical Oncology
Andreas Maus, Godefridus J Peters
Glioblastoma multiforme (GBM), or grade IV astrocytoma, is the most common type of primary brain tumor. It has a devastating prognosis with a 2-year-overall survival rate of only 26 % after standard treatment, which includes surgery, radiation, and adjuvant chemotherapy with temozolomide. Also lower grade gliomas are difficult to treat, because they diffusely spread into the brain, where extensive removal of tissue is critical. Better understanding of the cancer's biology is a key for the development of more effective therapy approaches...
October 17, 2016: Amino Acids
Ying Wang, Tao Liu, Ning Yang, Shuo Xu, Xingang Li, Donghai Wang
Glioblastoma (GBM) is a highly malignant brain tumor characterized by invasion tendency. Macrophage infiltration is associated with GBM invasion, but the mechanisms remain unclear. Hypoxia is an outstanding characteristic of GBM tissue. Hypoxia microenvironment modulates the biological behaviors of both tumor cells and infiltrated immune cells, including macrophages. In the present study, we analyzed the effects of hypoxia and macrophages on invasion of GBM cells and its potential mechanisms. We found that both hypoxia and macrophage supernatant promoted GBM cells invasion and matrix metalloproteinase (MMP)-9 expression, and hypoxia modulated the invasive activity of GBM cells by upregulating their CCR5 expression...
October 13, 2016: Oncology Reports
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