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https://www.readbyqxmd.com/read/28339833/vdac1-is-a-molecular-target-in-glioblastoma-with-its-depletion-leading-to-reprogrammed-metabolism-and-reversed-oncogenic-properties
#1
Tasleem Arif, Yakov Kerlin, Itay Nakdimon, Daniel Benharroch, Avijit Paul, Daniela Dadon-Klein, Varda Shoshan-Barmatz
Background.: Glioblastoma (GBM), an aggressive brain tumor with frequent relapses and a high mortality, still awaits an effective treatment. Like many cancers, GBM cells acquire oncogenic properties, including metabolic reprogramming, vital for growth. As such, tumor metabolism is an emerging avenue for cancer therapy. One relevant target is the voltage-dependent anion channel 1 (VDAC1), a mitochondrial protein controlling cell energy and metabolic homeostasis. Methods...
February 28, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/28338647/is-primary-prevention-with-antiepileptic-drugs-effective-in-brain-tumors-or-brain-metastases
#2
Diego Lobos-Urbina, Lucas Kittsteiner-Manubens, José Peña
Patients with brain tumors –primary or metastatic- have an increased risk of presenting seizures during the course of their disease. So, prophylactic antiepileptic drugs have been proposed. However, the effects of this intervention are not yet clear. To answer this question, we searched in Epistemonikos database, which is maintained by screening multiple databases. We identified 12 systematic reviews including 80 studies overall. Twelve corresponded to randomized trials, but only two answered the question of interest...
March 21, 2017: Medwave
https://www.readbyqxmd.com/read/28336375/tumortropic-adipose-derived-stem-cells-carrying-smart-nanotherapeutics-for-targeted-delivery-and-dual-modality-therapy-of-orthotopic-glioblastoma
#3
Wen-Chia Huang, I-Lin Lu, Wen-Hsuan Chiang, Yi-Wen Lin, Yuan-Chung Tsai, Hsin-Hung Chen, Chien-Wen Chang, Chi-Shiun Chiang, Hsin-Cheng Chiu
Chemotherapy is typically used to treat malignant brain tumors, especially for the tumors in surgically inaccessible areas. However, owing to the existence of blood-brain barrier (BBB), the tumor accumulation and therapeutic efficacy of clinical therapeutics is still of great concerns. To this end, we present herein a prominent therapeutic strategy adopting adipose-derived stem cells (ADSCs) capable of carrying nanotherapeutic payloads selectively toward brain tumors for thermo/chemotherapy. The nanoparticle (NP) payload was obtained from co-assembly of poly(γ-glutamic acid-co-distearyl γ-glutamate) with poly(lactic-co-glycolic acid), paclitaxel (PTX), and oleic acid-coated superparamagnetic iron oxide NPs in aqueous solution...
March 20, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28327947/factors-associated-with-pre-and-postoperative-seizures-in-1033-patients-undergoing-supratentorial-meningioma-resection
#4
William C Chen, Stephen T Magill, Dario J Englot, Joe D Baal, Sagar Wagle, Jonathan W Rick, Michael W McDermott
BACKGROUND: Risk factors for pre- and postoperative seizures in supratentorial meningiomas are understudied compared to other brain tumors. OBJECTIVE: To report seizure frequency and identify factors associated with pre- and postoperative seizures in a large single-center population study of patients undergoing resection of supratentorial meningioma. METHODS: Retrospective chart review of 1033 subjects undergoing resection of supratentorial meningioma at the author's institution (1991-2014)...
March 15, 2017: Neurosurgery
https://www.readbyqxmd.com/read/28326470/targeted-treatment-of-brain-metastases
#5
REVIEW
Nicole Shonka, Vyshak Alva Venur, Manmeet S Ahluwalia
PURPOSE OF REVIEW: Brain metastases are the most common intracranial tumors in adults. Historically, the median survival after the diagnosis of brain metastases has been dismal and medical therapies had a limited role in the management of these patients. RECENT FINDINGS: The advent of targeted therapy has ushered in an era of increased hope for patients with brain metastases. The most common malignancies that result in brain metastases-melanoma, lung cancer, and breast cancer, often have actionable mutations, which make them good candidates for targeted systemic therapy...
April 2017: Current Neurology and Neuroscience Reports
https://www.readbyqxmd.com/read/28320516/l-f001-a-novel-multifunctional-rock-inhibitor-suppresses-neuroinflammation-in-vitro-and-in-vivo-involvement-of-nf-%C3%AE%C2%BAb-inhibition-and-nrf2-pathway-activation
#6
Jingkao Chen, Wei Yin, Yalin Tu, Shengnan Wang, Xiaohong Yang, Qiuhe Chen, Xiao Zhang, Yifan Han, Rongbiao Pi
Microglia and astrocytes are largely responsible for inflammatory injury in the brain of Alzheimer's disease (AD). Increasing evidence has indicated that Rho kinase (ROCK) plays an important role in the regulation of neuroinflammation. Previously, we synthesized a new chemical entity L-F001 and proved its potential inhibitory effects on ROCK and oxidative stress. Here, we investigated the anti-inflammatory effects and the molecular mechanisms of L-F001 in vitro and in vivo. L-F001 remarkably suppressed lipopolysaccharides (LPS)-elevated expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) as well as LPS-induced production of nitric oxide (NO), reactive oxygen species, interleukin-6 (IL-6) and tumor necreactive oxygen speciesis factor-α (TNF-α) in microglial BV-2 cells and in cultured astrocytes...
March 16, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28319810/inhibitors-of-glut-slc2a-enhance-the-action-of-bcnu-and-temozolomide-against-high-grade-gliomas
#7
Alberto Azzalin, Giulia Nato, Elena Parmigiani, Francesca Garello, Annalisa Buffo, Lorenzo Magrassi
Glucose transport across glioblastoma membranes plays a crucial role in maintaining the enhanced glycolysis typical of high-grade gliomas and glioblastoma. We tested the ability of two inhibitors of the glucose transporters GLUT/SLC2A superfamily, indinavir (IDV) and ritonavir (RTV), and of one inhibitor of the Na/glucose antiporter type 2 (SGLT2/SLC5A2) superfamily, phlorizin (PHZ), in decreasing glucose consumption and cell proliferation of human and murine glioblastoma cells. We found in vitro that RTV, active on at least three different GLUT/SLC2A transporters, was more effective than IDV, a specific inhibitor of GLUT4/SLC2A4, both in decreasing glucose consumption and lactate production and in inhibiting growth of U87MG and Hu197 human glioblastoma cell lines and primary cultures of human glioblastoma...
March 17, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28315958/brain-tumor-location-influences-the-onset-of-acute-psychiatric-adverse-events-of-levetiracetam-therapy-an-observational-study
#8
Vincenzo Belcastro, Laura Rosa Pisani, Silvio Bellocchi, Paolo Casiraghi, Gaetano Gorgone, Marco Mula, Francesco Pisani
To explore possible correlations among brain lesion location, development of psychiatric symptoms and the use of antiepileptic drugs (AEDs) in a population of patients with brain tumor and epilepsy. The medical records of 283 patients with various types of brain tumor (161 M/122 F, mean age 64.9 years) were analysed retrospectively. Patients with grade III and IV glioma, previous history of epileptic seizures and/or psychiatric disorders were excluded. Psychiatric symptoms occurring after initiation of AED therapy were considered as treatment emergent psychiatric adverse events (TE-PAEs) if they fulfilled the following conditions: (1) onset within 4 weeks after the beginning of AED therapy; (2) disappearance on drug discontinuation; (3) absence of any other identified possible concurrent cause...
March 18, 2017: Journal of Neurology
https://www.readbyqxmd.com/read/28315063/the-effect-of-regadenoson-on-the-integrity-of-the-human-blood-brain-barrier-a-pilot-study
#9
Sadhana Jackson, Richard T George, Martin A Lodge, Anna Piotrowski, Richard L Wahl, Sachin K Gujar, Stuart A Grossman
Regadenoson is an FDA approved adenosine receptor agonist which increases blood-brain barrier (BBB) permeability in rodents. Regadenoson is used clinically for pharmacologic cardiac stress testing using SPECT or CT imaging agents that do not cross an intact BBB. This study was conducted to determine if standard doses of regadenoson transiently disrupt the human BBB allowing higher concentrations of systemically administered imaging agents to enter the brain. Patients without known intracranial disease undergoing clinically indicated pharmacologic cardiac stress tests were eligible for this study...
March 17, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28303493/the-effect-of-molecular-diagnostics-on-the-treatment-of-glioma
#10
REVIEW
Nancy Ann Oberheim Bush, Nicholas Butowski
PURPOSE OF REVIEW: This review summarizes the use of molecular diagnostics in glioma and its effect on the development of novel therapeutics and management decisions. RECENT FINDINGS: Genomic and proteomic profiling of brain tumors has provided significant expansion of our understanding of oncogenesis, characterization, and prognostication of brain tumors. Molecular markers such as MGMT, EGFR, IDH, 1p19q, ATRX, TERT, FGFR-TACC, and BRAF are now being used to classify brain tumors as well as influence management decisions...
April 2017: Current Oncology Reports
https://www.readbyqxmd.com/read/28298546/64cu-mm-302-positron-emission-tomography-quantifies-variability-of-enhanced-permeability-and-retention-of-nanoparticles-in-relation-to-treatment-response-in-patients-with-metastatic-breast-cancer
#11
Helen Lee, Anthony F Shields, Barry A Siegel, Kathy D Miller, Ian Krop, Cynthia X Ma, Patricia M LoRusso, Pamela N Munster, Karen Campbell, Daniel F Gaddy, Shannon C Leonard, Elena Geretti, Stephanie J Blocker, Dmitri B Kirpotin, Victor Moyo, Thomas J Wickham, Bart S Hendriks
PURPOSE: Therapeutic nanoparticles are designed to deliver their drug payloads through enhanced permeability and retention (EPR) in solid tumors. The extent of EPR and its variability in human tumors is highly debated and has been proposed as an explanation for variable responses to therapeutic nanoparticles in clinical studies. EXPERIMENTAL DESIGN: We assessed the EPR effect in patients using a 64Cu-labeled nanoparticle, 64Cu-MM-302 (64Cu-labeled HER2-targeted PEGylated liposomal doxorubicin), and imaging by Positron Emission Tomography/Computed Tomography (PET/CT)...
March 15, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28292827/the-glycoside-oleandrin-reduces-glioma-growth-with-direct-and-indirect-effects-on-tumor-cells
#12
Stefano Garofalo, Alfonso Grimaldi, Giuseppina Chece, Alessandra Porzia, Stefania Morrone, Fabrizio Mainiero, Giuseppina D'Alessandro, Vincenzo Esposito, Barbara Cortese, Silvia Di Angelantonio, Flavia Trettel, Cristina Limatola
Oleandrin is a glycoside that inhibits the ubiquitous enzyme Na(+)-K(+)-ATPase. In addition to its known effects on cardiac muscle, recent in vitro and in vivo evidence highlighted potential for anticancer properties of this compound. In this paper we evaluated for the first time the effect of oleandrin on brain tumors. To this aim mice were transplanted with human or murine glioma and analyzed for tumor progression upon oleandrin treatment. In both systems, oleandrin impaired glioma development, reduced tumor size, and inhibited cell proliferation...
March 14, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28292440/a-kinase-inhibitor-targeted-to-mtorc1-drives-regression-in-glioblastoma
#13
QiWen Fan, Ozlem Aksoy, Robyn A Wong, Shirin Ilkhanizadeh, Chris J Novotny, William C Gustafson, Albert Yi-Que Truong, Geraldine Cayanan, Erin F Simonds, Daphne Haas-Kogan, Joanna J Phillips, Theodore Nicolaides, Masanori Okaniwa, Kevan M Shokat, William A Weiss
Although signaling from phosphatidylinositol 3-kinase (PI3K) and AKT to mechanistic target of rapamycin (mTOR) is prominently dysregulated in high-grade glial brain tumors, blockade of PI3K or AKT minimally affects downstream mTOR activity in glioma. Allosteric mTOR inhibitors, such as rapamycin, incompletely block mTORC1 compared with mTOR kinase inhibitors (TORKi). Here, we compared RapaLink-1, a TORKi linked to rapamycin, with earlier-generation mTOR inhibitors. Compared with rapamycin and Rapalink-1, TORKi showed poor durability...
March 13, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28291423/preclinical-evaluation-of-convection-enhanced-delivery-of-liposomal-doxorubicin-to-treat-pediatric-diffuse-intrinsic-pontine-glioma-and-thalamic-high-grade-glioma
#14
A Charlotte P Sewing, Tonny Lagerweij, Dannis G van Vuurden, Michaël H Meel, Susanna J E Veringa, Angel M Carcaboso, Pieter J Gaillard, W Peter Vandertop, Pieter Wesseling, David Noske, Gertjan J L Kaspers, Esther Hulleman
OBJECTIVE Pediatric high-grade gliomas (pHGGs) including diffuse intrinsic pontine gliomas (DIPGs) are primary brain tumors with high mortality and morbidity. Because of their poor brain penetrance, systemic chemotherapy regimens have failed to deliver satisfactory results; however, convection-enhanced delivery (CED) may be an alternative mode of drug delivery. Anthracyclines are potent chemotherapeutics that have been successfully delivered via CED in preclinical supratentorial glioma models. This study aims to assess the potency of anthracyclines against DIPG and pHGG cell lines in vitro and to evaluate the efficacy of CED with anthracyclines in orthotopic pontine and thalamic tumor models...
February 17, 2017: Journal of Neurosurgery. Pediatrics
https://www.readbyqxmd.com/read/28290002/plasma-and-cerebrospinal-fluid-pharmacokinetics-of-select-chemotherapeutic-agents-following-intranasal-delivery-in-a-non-human-primate-model
#15
James C League-Pascual, Cynthia M Lester-McCully, Shaefali Shandilya, Lukas Ronner, Louis Rodgers, Rafael Cruz, Cody J Peer, William D Figg, Katherine E Warren
The blood-brain barrier (BBB) limits entry of most chemotherapeutic agents into the CNS, resulting in inadequate exposure within CNS tumor tissue. Intranasal administration is a proposed means of delivery that can bypass the BBB, potentially resulting in more effective chemotherapeutic exposure at the tumor site. The objective of this study was to evaluate the feasibility and pharmacokinetics (plasma and CSF) of intranasal delivery using select chemotherapeutic agents in a non-human primate (NHP) model. Three chemotherapeutic agents with known differences in CNS penetration were selected for intranasal administration in a NHP model to determine proof of principle of CNS delivery, assess tolerability and feasibility, and to evaluate whether certain drug characteristics were associated with increased CNS exposure...
March 13, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28288892/mr-image-guided-delivery-of-cisplatin-loaded-brain-penetrating-nanoparticles-to-invasive-glioma-with-focused-ultrasound
#16
Kelsie F Timbie, Umara Afzal, Abhijit Date, Clark Zhang, Ji Song, G Wilson Miller, Jung Soo Suk, Justin Hanes, Richard J Price
Systemically administered chemotherapeutic drugs are often ineffective in the treatment of invasive brain tumors due to poor therapeutic index. Within gliomas, despite the presence of heterogeneously leaky microvessels, dense extracellular matrix and high interstitial pressure generate a "blood-tumor barrier" (BTB), which inhibits drug delivery and distribution. Meanwhile, beyond the contrast MRI-enhancing edge of the tumor, invasive cancer cells are protected by the intact blood-brain barrier (BBB). Here, we tested whether brain-penetrating nanoparticles (BPN) that possess dense surface coatings of polyethylene glycol (PEG) and are loaded with cisplatin (CDDP) could be delivered across both the blood-tumor and blood-brain barriers with MR image-guided focused ultrasound (MRgFUS), and whether this treatment could control glioma growth and invasiveness...
March 11, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28283800/blocking-cox-2-induces-apoptosis-and-inhibits-cell-proliferation-via-the-akt-survivin-and-akt-id3-pathway-in-low-grade-glioma
#17
Aya Sato, Yoshifumi Mizobuchi, Kohei Nakajima, Kenji Shono, Toshitaka Fujihara, Teruyoshi Kageji, Keiko Kitazato, Kazuhito Matsuzaki, Hideo Mure, Kazuyuki Kuwayama, Akiko Sumi, Hideyuki Saya, Oltea Sampetrean, Shinji Nagahirao
Approximately half of surgically-treated patients with low-grade-glioma (LGG) suffer recurrence or metastasis. Currently there is no effective drug treatment. While the selective COX-2 inhibitor celecoxib showed anti-neoplastic activity against several malignant tumors, its effects against LGG remain to be elucidated. Ours is the first report that the expression level of COX-2 in brain tissue samples from patients with LGG and in LGG cell lines is higher than in the non-neoplastic region and in normal brain cells...
March 10, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28281497/management-of-brain-tumor-related-epilepsy
#18
REVIEW
Neil V Klinger, Aashit K Shah, Sandeep Mittal
Seizures are common in both primary and metastatic brain tumors, although the rate of seizures differ significantly between the different types of neoplasms. Patients with brain tumor-associated seizures need treatment with antiepileptic drugs (AEDs) to prevent recurrence, whereas strong clinical data exists to discourage routine prophylaxis in patients who have not had seizures. The newer AEDs, such as levetiracetam, lamotrigine, lacosamide, topiramate, or pregabalin, are preferable for various reasons, primarily related to the side-effect profile and limited interactions with other drugs...
2017: Neurology India
https://www.readbyqxmd.com/read/28280455/increasing-of-blood-brain-tumor-barrier-permeability-through-transcellular-and-paracellular-pathways-by-microbubble-enhanced-diagnostic-ultrasound-in-a-c6-glioma-model
#19
Jinlong Zhang, Heng Liu, Xuesong Du, Yu Guo, Xiao Chen, Shunan Wang, Jingqin Fang, Peng Cao, Bo Zhang, Zheng Liu, Weiguo Zhang
Most of the anticancer agents cannot be efficiently delivered into the brain tumor because of the existence of blood-brain tumor barrier (BTB). The objective of this study was to explore the effect of microbubble-enhanced diagnostic ultrasound (MEUS) on the BTB permeability and the possible mechanism. Glioma-bearing rats were randomized into three groups as follows: the microbubble-enhanced continued diagnostic ultrasound (MECUS) group; the microbubble-enhanced intermittent diagnostic ultrasound (MEIUS) group and the control group...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28279799/pbca-based-polymeric-microbubbles-for-molecular-imaging-and-drug-delivery
#20
Patrick Koczera, Lia Appold, Yang Shi, Mengjiao Liu, Anshuman Dasgupta, Vertika Pathak, Tarun Ojha, Stanley Fokong, Zhuojun Wu, Marc van Zandvoort, Olga Iranzo, Alexander Kuehne, Andrij Pich, Fabian Kiessling, Twan Lammers
Microbubbles (MB) are routinely used as contrast agents for ultrasound (US) imaging. We describe different types of targeted and drug-loaded poly(n-butyl cyanoacrylate) (PBCA) MB, and demonstrate their suitability for multiple biomedical applications, including molecular US imaging and US-mediated drug delivery. Molecular imaging of angiogenic tumor blood vessels and inflamed atherosclerotic endothelium is performed by modifying the surface of PBCA MB with peptides and antibodies recognizing E-selectin and VCAM-1...
March 6, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
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