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https://www.readbyqxmd.com/read/29334602/high-dose-metformin-plus-temozolomide-shows-increased-anti-tumor-effects-in-glioblastoma-in-vitro-and-in-vivo-compared-with-monotherapy
#1
Jung Eun Lee, Ji Hee Lim, Yong Kil Hong, Seung Ho Yang
Purpose: The purpose of the study is to investigate the efficacy of combined treatment with temozolomide (TMZ) and metformin for glioblastoma (GBM) in vitro and in vivo. Materials and Methods: We investigated the efficacy of combined treatment with TMZ and metformin using cell viability and apoptosis assays. A GBM orthotopic mice model was established by inoculation of 5x105 U87 cells and treated with metformin, TMZ, and the combination for 4 weeks. Western blotting and immunofluorescence of tumor specimens were analyzed to investigate AMP-activated protein kinase (AMPK) and AKT pathway...
January 10, 2018: Cancer Research and Treatment: Official Journal of Korean Cancer Association
https://www.readbyqxmd.com/read/29333924/dynamic-mr-imaging-for-functional-vascularization-depends-on-tissue-factor-signaling-in-glioblastoma
#2
Xiao Chen, Tian Xie, Jingqin Fang, Wei Xue, Houyi Kang, Haipeng Tong, Yu Guo, Bo Zhang, Sumei Wang, Yizeng Yang, Weiguo Zhang
Glomeruloid vascular proliferation (GVP) is a diagnostic hallmark and links to aggressive behavior, therapy resistance and poor prognosis in glioblastoma (GBM). It lacks clinical approaches to predict and monitor its formation and dynamic change. Yet the mechanism of GVPs also remains largely unknown. Using an in situ GBM xenograft mouse model, combined clinical MRI images of pre-surgery tumor and pathological investigation, we demonstrated that the inhibition of tissue factor (TF) decreased GVPs in Mouse GBM xenograft model...
January 15, 2018: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/29333657/gelatin-methacryloyl-hydrogels-in-the-absence-of-a-crosslinker-as-3d-glioblastoma-multiforme-gbm-mimetic-microenvironment
#3
Pelin Erkoc, Fidan Seker, Tugba Bagci-Onder, Seda Kizilel
3D platforms are important for monitoring tumor progression and screening drug candidates to eradicate tumors such as glioblastoma multiforme (GBM), a malignant type of human brain tumor. Here, a new strategy is reported that exploits visible-light-induced crosslinking of gelatin where the reaction is carried out in the absence of an additional crosslinker. Visible light-induced crosslinking promotes the design of cancer microenvironment-mimetic system without compromising the cell viability during the process and absence of crosslinker facilitates the synthesis of the unique construct...
January 15, 2018: Macromolecular Bioscience
https://www.readbyqxmd.com/read/29332185/handedness-and-the-risk-of-glioma
#4
Briana Miller, Noah C Peeri, Louis Burt Nabors, Jordan H Creed, Zachary J Thompson, Carrie M Rozmeski, Renato V LaRocca, Sajeel Chowdhary, Jeffrey J Olson, Reid C Thompson, Kathleen M Egan
Gliomas are the most common type of malignant primary brain tumor and few risk factors have been linked to their development. Handedness has been associated with several pathologic neurological conditions such as schizophrenia, autism, and epilepsy, but few studies have evaluated a connection between handedness and risk of glioma. In this study, we examined the relationship between handedness and glioma risk in a large case-control study (1849 glioma cases and 1354 healthy controls) and a prospective cohort study (326,475 subjects with 375 incident gliomas)...
January 13, 2018: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/29330749/toxicity-and-efficacy-of-lomustine-and-bevacizumab-in-recurrent-glioblastoma-patients
#5
J N Jakobsen, T Urup, K Grunnet, A Toft, M D Johansen, S H Poulsen, I J Christensen, A Muhic, H S Poulsen
The combination of lomustine and bevacizumab is a commonly used salvage treatment for recurrent glioblastoma (GBM). We investigated the toxicity and efficacy of lomustine plus bevacizumab (lom-bev) in a community-based patient cohort and made a comparison to another frequently used combination therapy consisting of irinotecan plus bevacizumab (iri-bev). Seventy patients with recurrent GBM were treated with lomustine 90 mg/m2 every 6 weeks and bevacizumab 10 mg/kg every 2 weeks. Toxicity was registered and compared to the toxicity observed in 219 recurrent GBM patients who had previously been treated with irinotecan 125 mg/m2 and bevacizumab 10 mg/kg every 2 weeks...
January 12, 2018: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/29330365/engineered-nanointerfaces-for-microfluidic-isolation-and-molecular-profiling-of-tumor-specific-extracellular-vesicles
#6
Eduardo Reátegui, Kristan E van der Vos, Charles P Lai, Mahnaz Zeinali, Nadia A Atai, Berent Aldikacti, Frederick P Floyd, Aimal H Khankhel, Vishal Thapar, Fred H Hochberg, Lecia V Sequist, Brian V Nahed, Bob S Carter, Mehmet Toner, Leonora Balaj, David T Ting, Xandra O Breakefield, Shannon L Stott
Extracellular vesicles (EVs) carry RNA, DNA, proteins, and lipids. Specifically, tumor-derived EVs have the potential to be utilized as disease-specific biomarkers. However, a lack of methods to isolate tumor-specific EVs has limited their use in clinical settings. Here we report a sensitive analytical microfluidic platform (EVHB-Chip) that enables tumor-specific EV-RNA isolation within 3 h. Using the EVHB-Chip, we achieve 94% tumor-EV specificity, a limit of detection of 100 EVs per μL, and a 10-fold increase in tumor RNA enrichment in comparison to other methods...
January 12, 2018: Nature Communications
https://www.readbyqxmd.com/read/29330078/intraoperative-flow-cytometry-enables-the-differentiation-of-primary-central-nervous-system-lymphoma-from-glioblastoma
#7
Shunichi Koriyama, Masayuki Nitta, Takahiro Shioyama, Takashi Komori, Takashi Maruyama, Takakazu Kawamata, Yoshihiro Muragaki
OBJECTIVE: Accurate preoperative and intraoperative differentiation between primary central nervous system lymphoma (PCNSL) and glioblastoma (GBM) is sometimes difficult. Distinguishing between these tumors during surgery is important because surgical treatment is different between the two tumors. In this study, we established a new method of intraoperative differentiation between PCNSL and GBM using intraoperative flow cytometry (iFC), and we retrospectively tested whether iFC was useful for the intraoperative diagnosis of PCNSL and GBM...
January 9, 2018: World Neurosurgery
https://www.readbyqxmd.com/read/29329273/transcriptomics-evidence-for-common-pathways-in-human-major-depressive-disorder-and-glioblastoma
#8
Yongfang Xie, Ling Wang, Zengyan Xie, Chuisheng Zeng, Kunxian Shu
Depression as a common complication of brain tumors. Is there a possible common pathogenesis for depression and glioma? The most serious major depressive disorder (MDD) and glioblastoma (GBM) in both diseases are studied, to explore the common pathogenesis between the two diseases. In this article, we first rely on transcriptome data to obtain reliable and useful differentially expressed genes (DEGs) by differential expression analysis. Then, we used the transcriptomics of DEGs to find out and analyze the common pathway of MDD and GBM from three directions...
January 12, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29328445/the-effects-of-interleukin-2-and-rad-p53-as-a-treatment-for-glioblastoma
#9
Hai-Bo Qiao, Jia Li, Lian-Jie Lv, Ben-Jin Nie, Peng Lu, Feng Xue, Zhi-Ming Zhang
Interleukin 2 (IL-2) is an anti-cancer cytokine that stimulates T cell propagation, triggering innate and adaptive immunity. IL-2 has been used for cancer therapy and has achieved curative effects. Recombinant adenovirus p53 injection (rAd‑p53) is a gene therapeutic agent that may improve the prognosis of patients with glioblastoma (GBM). In the present study, the effect of combined IL‑2 and rAd‑p53 treatment was studied. The ability of IL‑2 to stimulate immunoregulation and the ability of p53 to induce apoptosis for GBM was researched in the GBM tumor model...
January 9, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29328002/dexamethasone-mediated-oncogenicity-in-vitro-and-in-an-animal-model-of-glioblastoma
#10
Markus M Luedi, Sanjay K Singh, Jennifer C Mosley, Islam S A Hassan, Masumeh Hatami, Joy Gumin, Lukas Andereggen, Erik P Sulman, Frederick F Lang, Frank Stueber, Gregory N Fuller, Rivka R Colen, Pascal O Zinn
OBJECTIVE Dexamethasone, a known regulator of mesenchymal programming in glioblastoma (GBM), is routinely used to manage edema in GBM patients. Dexamethasone also activates the expression of genes, such as CEBPB, in GBM stem cells (GSCs). However, the drug's impact on invasion, proliferation, and angiogenesis in GBM remains unclear. To determine whether dexamethasone induces invasion, proliferation, and angiogenesis in GBM, the authors investigated the drug's impact in vitro, in vivo, and in clinical information derived from The Cancer Genome Atlas (TCGA) cohort...
January 12, 2018: Journal of Neurosurgery
https://www.readbyqxmd.com/read/29324911/psychological-consideration-in-patients-with-cerebral-gliomas-candidates-for-intra-operative-radiation-therapy-based-on-tumor-location
#11
Tohid Emami Meybodi, Masoumeh Najafi, Ali Keipourfard, Amir Nikouei, Afsoun Seddighi
OBJECTIVE: Intra-operative Radiation Therapy (IORT) is gaining popularity as an adjuvant option to surgical resection, in treatment of glioblastoma multiforme (GBM) for increasing survival rate, which a highly aggressive cerebral tumor with poor prognosis. Τhe authors plan to investigate the effects of IORT combined with surgical resection on the psychological status of these patients based on tumor location. SUBJECT AND METHODS: From December 2013 to February 2017, we have enrolled 109 patients with high grade cerebral gliomas, documented by Magnetic Resonance Spectroscopy (MRS)...
September 2017: Hellenic Journal of Nuclear Medicine
https://www.readbyqxmd.com/read/29322326/heparan-sulfate-accumulation-and-perlecan-hspg2-up-regulation-in-tumour-tissue-predict-low-relapse-free-survival-for-patients-with-glioblastoma
#12
Galina M Kazanskaya, Alexandra Y Tsidulko, Alexander M Volkov, Roman S Kiselev, Anastasia V Suhovskih, Vyacheslav V Kobozev, Alexei S Gaytan, Svetlana V Aidagulova, Alexei L Krivoshapkin, Elvira V Grigorieva
Glycosaminoglycans are major components of brain extracellular matrix (ECM), although heparan sulfate (HS) contribution in brain physiology and carcinogenesis remains underinvestigated. This study examined HS content and distribution in glioblastoma multiforme (GBM) tissues in the context of potential molecular mechanisms underlying its deregulation in brain tumours. Totally, 42 tissue samples and paraffin-embedded tissues for 31 patients with different prognosis were investigated. HS expression was demonstrated in 50-55% of the GBM tumours by immunohistochemistry (IHC), while almost no HS content was detected in the surrounding paratumourous brain tissues...
January 10, 2018: Histochemistry and Cell Biology
https://www.readbyqxmd.com/read/29321665/fhl2-interacts-with-egfr-to-promote-glioblastoma-growth
#13
Lili Sun, Shuye Yu, Hui Xu, Yanwen Zheng, Juntang Lin, Meiyan Wu, Jide Wang, Aidong Wang, Qing Lan, Frank Furnari, Webster Cavenee, Benjamin Purow, Ming Li
Four-and-a-half LIM protein2 (FHL2) is a member of the LIM-only protein family, which plays a critical role in tumorigenesis. We previously reported that FHL2 is upregulated and plays an oncogenic role in glioblastoma (GBM), the most common and aggressive brain tumor. GBM is also marked by amplification of the epidermal growth factor receptor (EGFR) gene and its mutations, of which EGFRvIII is the most common and functionally significant. Here we report that FHL2 physically interacts with the wild-type EGFR and its mutated EGFRvIII form in GBM cells...
January 11, 2018: Oncogene
https://www.readbyqxmd.com/read/29321663/lpa-signaling-is-regulated-through-the-primary-cilium-a-novel-target-in-glioblastoma
#14
Yuriy V Loskutov, Caryn L Griffin, Kristina M Marinak, Andrey Bobko, Naira V Margaryan, Werner J Geldenhuys, Jann N Sarkaria, Elena N Pugacheva
The primary cilium is a ubiquitous organelle presented on most human cells. It is a crucial signaling hub for multiple pathways including growth factor and G-protein coupled receptors. Loss of primary cilia, observed in various cancers, has been shown to affect cell proliferation. Primary cilia formation is drastically decreased in glioblastoma (GBM), however, the role of cilia in normal astrocyte or glioblastoma proliferation has not been explored. Here, we report that loss of primary cilia in human astrocytes stimulates growth rate in a lysophosphatidic acid (LPA)-dependent manner...
January 11, 2018: Oncogene
https://www.readbyqxmd.com/read/29321659/epidermal-growth-factor-receptor-and-egfrviii-in-glioblastoma-signaling-pathways-and-targeted-therapies
#15
REVIEW
Zhenyi An, Ozlem Aksoy, Tina Zheng, Qi-Wen Fan, William A Weiss
Amplification of epidermal growth factor receptor (EGFR) and its active mutant EGFRvIII occurs frequently in glioblastoma (GBM). While EGFR and EGFRvIII play critical roles in pathogenesis, targeted therapy with EGFR-tyrosine kinase inhibitors (TKIs) or antibodies has only shown limited efficacy in patients. Here we discuss signaling pathways mediated by EGFR/EGFRvIII, current therapeutics, and novel strategies to target EGFR/EGFRvIII-amplified GBM.
January 11, 2018: Oncogene
https://www.readbyqxmd.com/read/29319175/bk-channels-blockage-inhibits-hypoxia-induced-migration-and-chemoresistance-to-cisplatin-in-human-glioblastoma-cells
#16
Paolo Rosa, Luigi Catacuzzeno, Luigi Sforna, Giorgio Mangino, Silvia Carlomagno, Gabriella Mincione, Vincenzo Petrozza, Giuseppe Ragona, Fabio Franciolini, Antonella Calogero
Glioblastoma (GBM) cells express large-conductance, calcium-activated potassium (BK) channels, whose activity is important for several critical aspects of the tumor, such as migration/invasion and cell death. GBMs are also characterized by a heavy hypoxic microenvironment that exacerbates tumor aggressiveness. Since hypoxia modulates the activity of BK channels in many tissues, we hypothesized that a hypoxia-induced modulation of these channels may contribute to the hypoxia-induced GBM aggressiveness. In U87-MG cells, hypoxia induced a functional upregulation of BK channel activity, without interfering with their plasma membrane expression...
January 10, 2018: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29318454/gl261-glioma-tumor-cells-respond-to-atp-with-an-intracellular-calcium-rise-and-glutamate-release
#17
Averey D Strong, M Caitlin Indart, Nolan R Hill, Richard L Daniels
Glioblastoma (GBM) is an aggressive brain cancer with an average survival rate of 15 months. The composition of the GBM tumor microenvironment-its pH, the presence of growth and immune factors, neurotransmitters, and gliotransmitters-plays an important role in GBM pathophysiology and facilitates tumor survival and growth. In particular, GBM tumor cells produce glutamate, which is toxic to healthy tissue and is associated with increased tumor invasion into adjacent brain regions. The conditions that lead to this excitotoxic release of glutamate are not completely understood...
January 9, 2018: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/29316219/characterization-of-a-foxg1-tle1-transcriptional-network-in-glioblastoma-initiating-cells
#18
Rola Dali, Federica Verginelli, Albena Pramatarova, Robert Sladek, Stefano Stifani
Glioblastoma (GBM) is the most common and deadly malignant brain cancer of glial cell origin, with a median patient survival of less than 20 months. Transcription factors FOXG1 and TLE1 promote GBM propagation by supporting maintenance of brain tumour initiating cells with stem-like properties. Here, we characterize FOXG1 and TLE1 target genes in glioblastoma patient-derived brain tumour initiating cells using ChIP-Seq and RNA-Seq approaches. These studies identify 150 direct FOXG1 targets, several of which are also TLE1 targets, involved in cell proliferation, differentiation, survival, chemotaxis and angiogenesis...
January 9, 2018: Molecular Oncology
https://www.readbyqxmd.com/read/29313975/near-infrared-photoimmunotherapy-targeting-egfr-shedding-new-light-on-glioblastoma-treatment
#19
Thomas A Burley, Justyna Mączyńska, Anant Shah, Wojciech Szopa, Kevin J Harrington, Jessica K R Boult, Anna Mrozek-Wilczkiewicz, Maria Vinci, Jeffrey C Bamber, Wojciech Kaspera, Gabriela Kramer-Marek
Glioblastomas (GBM) are high-grade brain tumours, differentially driven by alterations (amplification, deletion, or missense mutations) in the epidermal growth factor receptor (EGFR), that carry a poor prognosis of just 12-15 months following standard therapy. A combination of interventions targeting tumor-specific cell surface regulators along with convergent downstream signalling pathways may enhance treatment efficacy. Against this background, we investigated a novel photoimmunotherapy approach combining the cytotoxicity of photodynamic therapy with the specificity of immunotherapy...
January 5, 2018: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29313411/inhibition-of-wnt-ctnnb1-signaling-upregulates-sqstm1-and-sensitizes-glioblastoma-cells-to-autophagy-blockers
#20
Mireia Nager, Marta Crespí Sallán, Anna Visa, Charumathi Pushparaj, Maria Santacana, Anna Macià, Andrée Yeramian, Carles Cantí, Judit Herreros
WNT-CTNN1B signaling promotes cancer cell proliferation and stemness. Furthermore, recent evidence indicates that macroautophagy/autophagy regulates WNT signaling. Here we investigated the impact of inhibiting WNT signaling on autophagy in glioblastoma (GBM), a devastating brain tumor. Inhibiting TCF, or silencing TCF4 or CTNNB1/β-catenin upregulated SQSTM1/p62 in GBM at transcriptional and protein levels and, in turn, autophagy. DKK1/Dickkopf1, a canonical WNT receptor antagonist, also induced autophagic flux...
January 9, 2018: Autophagy
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