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https://www.readbyqxmd.com/read/29352318/temozolomide-induced-increase-of-tumorigenicity-can-be-diminished-by-targeting-of-mitochondria-in-in-vitro-models-of-patient-individual-glioblastoma
#1
Doreen William, Madlin Walther, Björn Schneider, Michael Linnebacher, Carl Friedrich Classen
Glioblastoma multiforme (GBM) is a highly heterogeneous and aggressive brain tumor with a dismal prognosis. Development of resistance towards cytostatic drugs like the GBM standard drug temozolomide is a severe problem in GBM treatment. One potential source of GBM relapse could be so called cancer stem like cells (CSCs). These represent an undifferentiated subpopulation of cells with high potential for tumor initiation. Furthermore, it has been shown that differentiated GBM cells can regain CSC properties when exposed to continuous temozolomide treatment in vitro...
2018: PloS One
https://www.readbyqxmd.com/read/29351056/remediation-of-radiation-induced-cognitive-dysfunction-through-oral-administration-of-the-neuroprotective-compound-nsi-189
#2
Barrett Allen, Munjal M Acharya, Celine Lu, Erich Giedzinski, Nicole Chmielewski, David Quach, Mike Hefferan, Karl K Johe, Charles L Limoli
Clinical management of primary and secondary central nervous system (CNS) malignancies frequently includes radiotherapy to forestall tumor growth and recurrence after surgical resection. While cranial radiotherapy remains beneficial, adult and pediatric brain tumor survivors suffer from a wide range of debilitating and progressive cognitive deficits. Although this has been recognized as a significant problem for decades, there remains no clinical recourse for the unintended neurocognitive sequelae associated with these types of cancer treatments...
January 19, 2018: Radiation Research
https://www.readbyqxmd.com/read/29349577/combination-therapy-with-sulfasalazine-and-valproic-acid-promotes-human-glioblastoma-cell-death-through-imbalance-of-the-intracellular-oxidative-response
#3
Carlos Gustavo Garcia, Suzana Assad Kahn, Luiz Henrique Medeiros Geraldo, Igor Romano, Ivan Domith, Deborah Christinne Lima E Silva, Fernando Dos Santos Assunção, Marcos José Ferreira, Camila Cabral Portugal, Jorge Marcondes de Souza, Luciana Ferreira Romão, Annibal Duarte Pereira Netto, Flávia Regina Souza Lima, Marcelo Cossenza
Glioblastoma (GBM) is the most common and aggressive malignant primary brain tumor and still lacks effective therapeutic strategies. It has already been shown that old drugs like sulfasalazine (SAS) and valproic acid (VPA) present antitumoral activities in glioma cell lines. SAS has also been associated with a decrease of intracellular glutathione (GSH) levels through a potent inhibition of xc- glutamate/cystine exchanger leading to an antioxidant deprotection. In the same way, VPA was recently identified as a histone deacetylase (HDAT) inhibitor capable of activating tumor suppression genes...
January 19, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29348889/metformin-and-temozolomide-a-synergic-option-to-overcome-resistance-in-glioblastoma-multiforme-models
#4
Silvia Valtorta, Alessia Lo Dico, Isabella Raccagni, Daniela Gaglio, Sara Belloli, Letterio S Politi, Cristina Martelli, Cecilia Diceglie, Marcella Bonanomi, Giulia Ercoli, Valentina Vaira, Luisa Ottobrini, Rosa Maria Moresco
Glioblastoma multiforme (GBM) is the most aggressive primary brain tumor with poor survival. Cytoreduction in association with radiotherapy and temozolomide (TMZ) is the standard therapy, but response is heterogeneous and life expectancy is limited. The combined use of chemotherapeutic agents with drugs targeting cell metabolism is becoming an interesting therapeutic option for cancer treatment. Here, we found that metformin (MET) enhances TMZ effect on TMZ-sensitive cell line (U251) and overcomes TMZ-resistance in T98G GBM cell line...
December 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29348854/acid-ceramidase-and-its-inhibitors-a-de-novo-drug-target-and-a-new-class-of-drugs-for-killing-glioblastoma-cancer-stem-cells-with-high-efficiency
#5
Ninh B Doan, Hisham Alhajala, Mona M Al-Gizawiy, Wade M Mueller, Scott D Rand, Jennifer M Connelly, Elizabeth J Cochran, Christopher R Chitambar, Paul Clark, John Kuo, Kathleen M Schmainda, Shama P Mirza
Glioblastoma remains the most common, malignant primary cancer of the central nervous system with a low life expectancy and an overall survival of less than 1.5 years. The treatment options are limited and there is no cure. Moreover, almost all patients develop recurrent tumors, which typically are more aggressive. Therapeutically resistant glioblastoma or glioblastoma stem-like cells (GSCs) are hypothesized to cause this inevitable recurrence. Identifying prognostic biomarkers of glioblastoma will potentially advance knowledge about glioblastoma tumorigenesis and enable discovery of more effective therapies...
December 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29345190/magnetoelectric-nanoparticles-for-delivery-of-antitumor-peptides-into-glioblastoma-cells-by-magnetic-fields
#6
Tiffanie S Stewart, Abhignyan Nagesetti, Rakesh Guduru, Ping Liang, Emmanuel Stimphil, Ali Hadjikhani, Luis Salgueiro, Jeffrey Horstmyer, Renzhi Cai, Andrew Schally, Sakhrat Khizroev
AIM: We studied externally controlled anticancer effects of binding tumor growth inhibiting synthetic peptides to magnetoelectric nanoparticles (MENs) on treatment of glioblastomas. METHODS: Hydrothermally synthesized 30-nm MENs had the core-shell composition of CoFe2O4@BaTiO3. Molecules of growth hormone-releasing hormone antagonist of the MIA class (MIA690) were chemically bound to MENs. In vitro experiments utilized human glioblastoma cells (U-87MG) and human brain microvascular endothelial cells...
January 18, 2018: Nanomedicine
https://www.readbyqxmd.com/read/29343521/t-type-ca2-channels-t-for-targetable
#7
REVIEW
Marta C Sallán, Anna Visa, Soni Shaikh, Mireia Nàger, Judit Herreros, Carles Cantí
In the past decade, T-type Ca2+ channels (TTCC) have been unveiled as key regulators of cancer cell biology and thus have been proposed as chemotherapeutic targets. Indeed, in vitro and in vivo studies indicate that TTCC pharmacologic blockers have a negative impact on the viability of cancer cells and reduce tumor size, respectively. Consequently mibefradil, a TTCC blocker approved in 1997 as an antihypertensive agent but withdrawn in 1998 because of drug-drug interactions, was granted 10 years later the orphan drug status by the FDA to investigate its efficacy against brain, ovary, and pancreatic cancer...
January 17, 2018: Cancer Research
https://www.readbyqxmd.com/read/29342193/analysis-of-copy-number-loss-of-the-erbb4-receptor-tyrosine-kinase-in-glioblastoma
#8
DeAnalisa C Jones, Adriana Scanteianu, Matthew DiStefano, Mehdi Bouhaddou, Marc R Birtwistle
Current treatments for glioblastoma multiforme (GBM)-an aggressive form of brain cancer-are minimally effective and yield a median survival of 14.6 months and a two-year survival rate of 30%. Given the severity of GBM and the limitations of its treatment, there is a need for the discovery of novel drug targets for GBM and more personalized treatment approaches based on the characteristics of an individual's tumor. Most receptor tyrosine kinases-such as EGFR-act as oncogenes, but publicly available data from the Cancer Cell Line Encyclopedia (CCLE) indicates copy number loss in the ERBB4 RTK gene across dozens of GBM cell lines, suggesting a potential tumor suppressor role...
2018: PloS One
https://www.readbyqxmd.com/read/29340013/the-small-molecule-si113-synergizes-with-mitotic-spindle-poisons-in-arresting-the-growth-of-human-glioblastoma-multiforme
#9
Claudia Abbruzzese, Giada Catalogna, Enzo Gallo, Simona di Martino, Anna M Mileo, Mariantonia Carosi, Vincenzo Dattilo, Silvia Schenone, Francesca Musumeci, Patrizia Lavia, Nicola Perrotti, Rosario Amato, Marco G Paggi
Glioblastoma multiforme (GBM) is the deadliest brain tumor. State-of-art GBM therapy often fails to ensure control of a disease characterized by high frequency of recurrences and progression. In search for novel therapeutic approaches, we assayed the effect of compounds from a cancer drug library on the ADF GBM cell line, establishing their elevated sensitivity to mitotic spindle poisons. Our previous work showed that the effectiveness of the spindle poison paclitaxel in inhibiting cancer cell growth was dependent on the expression of RANBP1, a regulatory target of the serine/threonine kinase SGK1...
December 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29336268/%C3%AE-naplastic-lymphoma-kinase-in-glioblastoma-detection-diagnostic-methods-and-therapeutic-options
#10
Theodosis Kalamatianos, Despoina Denekou, George Stranjalis, Evangelia Papadimitriou
BACKGROUND: Glioblastoma (GBM) is the most aggressive and common brain tumor in adults, currently lacking effective life-prolonging and recurrence-preventing therapy; median survival of GBM patients stands at only 14-16 months. Increasing lines of evidence indicate that Anaplastic lymphoma kinase (ALK), a druggable tyrosine kinase receptor over-expressed in GBM, represents a potential therapeutic target in this tumor. OBJECTIVE: An overview of the state of the art and the existing recent patents regarding potential exploitation of ALK as a therapeutic target and/or diagnostic/prognostic factor in GBM...
January 15, 2018: Recent Patents on Anti-cancer Drug Discovery
https://www.readbyqxmd.com/read/29333657/gelatin-methacryloyl-hydrogels-in-the-absence-of-a-crosslinker-as-3d-glioblastoma-multiforme-gbm-mimetic-microenvironment
#11
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/29333521/nanomaterials-for-convection-enhanced-delivery-of-agents-to-treat-brain-tumors
#12
Young-Eun Seo, Tom Bu, W Mark Saltzman
Nanomaterials represent a promising and versatile platform for the delivery of therapeutics to the brain. Treatment of brain tumors has been a long-standing challenge in the field of neuro-oncology. The current standard of care - a multimodal approach of surgery, radiation and chemotherapy - yields only a modest therapeutic benefit for patients with malignant gliomas. A major obstacle for treatment is the failure to achieve sufficient delivery of therapeutics at the tumor site. Recent advances in local drug delivery techniques, along with the development of highly effective brain-penetrating nanocarriers, have significantly improved treatment and imaging of brain tumors in preclinical studies...
December 2017: Current Opinion in Biomedical Engineering
https://www.readbyqxmd.com/read/29332604/the-effect-of-an-adenosine-a2a-agonist-on-intra-tumoral-concentrations-of-temozolomide-in-patients-with-recurrent-glioblastoma
#13
Sadhana Jackson, Jon Weingart, Edjah K Nduom, Thura T Harfi, Richard T George, Dorothea McAreavey, Xiaobu Ye, Nicole M Anders, Cody Peer, William D Figg, Mark Gilbert, Michelle A Rudek, Stuart A Grossman
BACKGROUND: The blood-brain barrier (BBB) severely limits the entry of systemically administered drugs including chemotherapy to the brain. In rodents, regadenoson activation of adenosine A2A receptors causes transient BBB disruption and increased drug concentrations in normal brain. This study was conducted to evaluate if activation of A2A receptors would increase intra-tumoral temozolomide concentrations in patients with glioblastoma. METHODS: Patients scheduled for a clinically indicated surgery for recurrent glioblastoma were eligible...
January 15, 2018: Fluids and Barriers of the CNS
https://www.readbyqxmd.com/read/29332078/magnetic-resonance-guided-high-intensity-focused-ultrasound-for-treating-movement-disorders
#14
Young Goo Kim, Eun Jung Kweon, Won Seok Chang, Hyun Ho Jung, Jin Woo Chang
Transcranial magnetic resonance-guided focused ultrasound (MRgFUS) surgery has recently gained favor as a novel, noninvasive alternative to conventional neurosurgery. In contrast to traditional ablative interventions, transcranial MRgFUS surgery is entirely imaging-guided and uses continuous temperature measurements at the target and surrounding tissue taken in real-time. Unlike Gamma Knife radiosurgery, MRgFUS surgery can make a lesion immediately and does not use ionizing radiation. Moreover, since no metallic device is implanted, MR imaging-based diagnosis is not restricted throughout life...
2018: Progress in Neurological Surgery
https://www.readbyqxmd.com/read/29328000/conscious-sedation-with-dexmedetomidine-compared-with-asleep-awake-asleep-craniotomies-in-glioma-surgery-an-analysis-of-180-patients
#15
Eric Suero Molina, Stephanie Schipmann, Isabelle Mueller, Johannes Wölfer, Christian Ewelt, Matthias Maas, Benjamin Brokinkel, Walter Stummer
OBJECTIVE Awake craniotomies have become a feasible tool over time to treat brain tumors located in eloquent regions. Different techniques have been applied in neurooncology centers. Both "asleep-awake-asleep" (asleep) and "conscious sedation" were used subsequently at the authors' neurosurgical department. Since 2013, the authors have only performed conscious sedation surgeries, predominantly using the α2-receptor agonist dexmedetomidine as the anesthetic drug. The aim of this study was to compare both mentioned techniques and evaluate the clinical use of dexmedetomidine in the setting of awake craniotomies for glioma surgery...
January 12, 2018: Journal of Neurosurgery
https://www.readbyqxmd.com/read/29322843/immunotherapy-for-brain-tumors-understanding-early-successes-and-limitations
#16
Nicole A P Lieberman, Nicholas A Vitanza, Courtney A Crane
Adverse effects and toxicities related to standard treatments for brain tumors significantly reduce patients' quality of life. Although most immunotherapy approaches for solid tumors have not been successful, several early-phase clinical trials are beginning to reveal a potential role for immunotherapy in the treatment of brain tumors. In particular, methods that activate the innate immune system and induce a polyclonal anti-cancer response have demonstrated that brain tumors are susceptible to immune-mediated tumor destruction...
January 11, 2018: Expert Review of Neurotherapeutics
https://www.readbyqxmd.com/read/29315660/precision-and-bias-of-target-controlled-prolonged-propofol-infusion-for-general-anesthesia-and-sedation-in-neurosurgical-patients
#17
Andrea Cortegiani, Alessandra Pavan, Fabio Azzeri, Giuseppe Accurso, Filippo Vitale, Cesare Gregoretti
The aim of this study was to determine the relationship, precision, and bias of a propofol target-controlled infusion (TCI) system during prolonged infusion in neurosurgical patients. We retrospectively included patients undergoing general anesthesia for elective neurosurgical removal of brain tumors and postoperative sedation in the intensive care unit over a period of 3 months. TCI of propofol (Diprifusor - Marsh model) and remifentanil were used for general anesthesia and sedation. We compared propofol blood concentration (Cmeas ) measured by liquid chromatography-mass spectroscopy with predicted concentrations (Cpred ) by the TCI system at 40 minutes (T0), 2 hours (T1), and 4 hours (T2) and every 8 hours after starting the drug infusion and at the time of emergence from sedation...
January 9, 2018: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/29301833/establishing-a-preclinical-multidisciplinary-board-for-brain-tumors
#18
Birgit Nimmervoll, Nidal Boulos, Brandon M Bianski, Jason Dapper, Michael DeCuypere, Anang A Shelat, Sabrina Terranova, Hope Elizabeth Terhune, Amar Gajjar, Yogesh T Patel, Burgess B Freeman, Arzu Onar-Thomas, Clinton F Stewart, Martine F Roussel, R Kiplin Guy, Thomas E Merchant, Christopher Calabrese, Karen D Wright, Richard J Gilbertson
PURPOSE: Curing all children with brain tumors will require an understanding of how each subtype responds to conventional treatments and how best to combine existing and novel therapies.  It is extremely challenging to acquire this knowledge in the clinic alone, especially among patients with rare tumors.  Therefore, we developed a preclinical brain tumor platform to test combinations of conventional and novel therapies in a manner that closely recapitulates clinic trials.  Experimental Design: A multidisciplinary team was established to design and conduct neurosurgical, fractionated radiotherapy and chemotherapy studies, alone or in combination, in accurate mouse models of supratentorial ependymoma (SEP) subtypes and choroid plexus carcinoma (CPC)...
January 4, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29301599/experimental-study-on-the-protection-of-agrimony-extracts-from-different-extracting-methods-against-cerebral-ischemia-reperfusion-injury
#19
Hui-Yuan Zhu, Yu-Long Bie, Jiang Wang, Jing Gao, Bing-Yue Yang, Hai-Tong Wan
Objective To study the protective effect of agrimony extracts from different extracting methods on cerebral ischemia-reperfusion injury in rats, in order to optimize the extraction scheme of agrimony. Methods Male rats were randomly assigned into seven groups: 1. Sham-operated group, 2. Untreated MCAO group (MCAO), 3. Petroleum ether extract of Agrimonia pilosa treated MCAO group (PEA), 4. Ethyl acetate extract of Agrimonia pilosa treated MCAO group (EAEA), 5. Ethanol extract of Agrimonia pilosa treated MCAO group (EEA), 6...
December 30, 2017: Chinese Medical Sciences Journal, Chung-kuo i Hsüeh K'o Hsüeh Tsa Chih
https://www.readbyqxmd.com/read/29301276/rosiglitazone-as-a-modulator-of-tlr4-and-tlr3-signaling-pathways-in-rat-primary-neurons-and-astrocytes
#20
Dmitry V Chistyakov, Nadezda V Azbukina, Alexandr V Lopachev, Ksenia N Kulichenkova, Alina A Astakhova, Marina G Sergeeva
An antidiabetic drug of the thiazolidinedione class, rosiglitazone (RG) demonstrates anti-inflammatory properties in various brain pathologies. The mechanism of RG action in brain cells is not fully known. To unravel mechanisms of RG modulation of toll-like receptor (TLR) signaling pathways, we compare primary rat neuron and astrocyte cultures stimulated with the TLR4 agonist lipopolysaccharide (LPS) and the TLR3 agonist poly I:C (PIC). Both TLR agonists induced tumor necrosis factor (TNFα) release in astrocytes, but not in neurons...
January 2, 2018: International Journal of Molecular Sciences
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