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https://www.readbyqxmd.com/read/28445970/acid-ceramidase-is-a-novel-drug-target-for-pediatric-brain-tumors
#1
Ninh B Doan, Ha S Nguyen, Andrew Montoure, Mona M Al-Gizawiy, Wade M Mueller, Shekar Kurpad, Scott D Rand, Jennifer M Connelly, Christopher R Chitambar, Kathleen M Schmainda, Shama P Mirza
Pediatric brain tumors are the most common solid tumors in children and are also a leading culprit of cancer-related fatalities in children. Pediatric brain tumors remain hard to treat. In this study, we demonstrated that medulloblastoma, pediatric glioblastoma, and atypical teratoid rhabdoid tumors express significant levels of acid ceramidase, where levels are highest in the radioresistant tumors, suggesting that acid ceramidase may confer radioresistance. More importantly, we also showed that acid ceramidase inhibitors are highly effective at targeting these pediatric brain tumors with low IC50 values (4...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28442918/targeting-the-pd-1-pathway-in-pediatric-solid-tumors-and-brain-tumors
#2
REVIEW
Lars M Wagner, Val R Adams
While remarkable advances have been made in the treatment of pediatric leukemia over the past decades, new therapies are needed for children with advanced solid tumors and high-grade brain tumors who fail standard chemotherapy regimens. Immunotherapy with immune checkpoint inhibitors acting through the programmed cell death-1 (PD-1) pathway has shown efficacy in some chemotherapy-resistant adult cancers, generating interest that these agents may also be helpful to treat certain refractory pediatric malignancies...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28442538/peripheral-tumor-necrosis-factor-alpha-tnf-%C3%AE-modulates-amyloid-pathology-by-regulating-blood-derived-immune-cells-and-glial-response-in-the-brain-of-ad-tnf-transgenic-mice
#3
Evi Paouri, Ourania Tzara, Georgia-Ioanna Kartalou, Sofia Zenelak, Spiros Georgopoulos
Increasing evidence has suggested that systemic inflammation along with local brain inflammation can play a significant role in Alzheimer's disease (AD) pathogenesis. Identifying key molecules that regulate the crosstalk between the immune and the central nervous system can provide potential therapeutic targets. TNF-α is a pro-inflammatory cytokine implicated in the pathogenesis of systemic inflammatory and neurodegenerative diseases such as rheumatoid arthritis (RA) and AD. Recent studies have reported that anti-TNF-α therapy or RA itself can modulate AD pathology, although the underlying mechanism is unclear...
April 25, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28440967/toxicity-of-cisplatin-loaded-poly-butyl-cyanoacrylate-nanoparticles-in-a-brain-cancer-cell-line-anionic-polymerization-results
#4
Nejad Mohamadi, S Maryam Kazemi, Mahshid Mohammadian, Attabak Toofani Milani, Younes Moradi, Maryam Yasemi, Meysam Ebrahimi far, Maral Mazloumi Tabrizi, Hasan Ebrahimi Shahmabadi, Azim Akbarzadeh Khiyavi
Cancer is one of the most important issues in modern medicine and the most common cause of death after cardiovascular diseases in many countries. Brain cancer is one of the most common causes of cancer death among men and women, ranking third. Chemotherapeutic drugs that aim to prevent uncontrolled proliferation of cells in tissues of the body and induce apoptosis of tumor cells are prominent candidates for development. Since cisplatin has an apoptosisinducing role, it is widely used as an anticancer agent...
March 1, 2017: Asian Pacific Journal of Cancer Prevention: APJCP
https://www.readbyqxmd.com/read/28434806/fibronectin-adherent-peripheral-blood-derived-mononuclear-cells-as-paclitaxel-carriers-for-glioblastoma-treatment-an-in-vitro-study
#5
Marco Paolo Schiariti, Francesco Restelli, Paolo Ferroli, Anna Benetti, Angiola Berenzi, Anna Ferri, Valentina Ceserani, Emilio Ciusani, Moris Cadei, Gaetano Finocchiaro, Augusto Pessina, Eugenio Parati, Roberto Pallini, Giulio Alessandri
BACKGROUND: Glioblastoma (GBM) represents the most aggressive malignant brain tumor in adults, with a risible median life expectancy despite gold standard treatment. Novel drug-delivery methods have been explored. Here we evaluated the possibility to use mononuclear cells (MCs) belonging to the monocytic-dendritic lineage as drug-carrier. METHODS: MCs were obtained from 10 patients harboring a GBM, and from healthy volunteers, considered as controls. GBM tissue was also obtained from patients...
April 20, 2017: Cytotherapy
https://www.readbyqxmd.com/read/28430288/mesenchymal-proangiogenic-factor-ykl-40-related-to-glioblastomas-and-its-relationship-with-the-subventricular-zone
#6
Kelvin M Pińa Batista, Sayoa Alvarez de Eulate-Beramendi, Kenia Y Álvarez Reyes de Pińa, Pedro Reimunde Figueira, Adan Fernandez Canal, Josué M Avecillas Chasin, Ángela Meilan, Rodrigo Ugalde, Ivan Fernandez Vega
<i>Glioblastoma is the most common primary brain tumor. Despite multimodality therapy with aggressive microsurgical resection and adjuvant chemotherapy and radiotherapy, the median survival is below 15 months. Glioblastomas are heterogeneous tumors with high resistance to most chemotherapeutic drugs. According to reliable evidence, YKL-40, one of the best investigated chitinase-like protein, may facilitate invasion, migration and angiogenesis, and could be also responsible for temozolomide resistance in glioblastoma, thus conferring a dismal prognosis...
2017: Folia Neuropathologica
https://www.readbyqxmd.com/read/28429235/regulation-of-human-brain-microvascular-endothelial-cell-adhesion-and-barrier-functions-by-memantine
#7
Fei Wang, Zhirong Zou, Yi Gong, Dong Yuan, Xun Chen, Tao Sun
Vascular risk factors have been linked to cognitive decline and dementia in the elderly. Microvascular inflammation, especially of the endothelium, may contribute to the progression of neurodegenerative events in Alzheimer's disease (AD). Memantine, an uncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist, is a licensed drug used for the treatment of moderate to severe AD. However, little information is available regarding its anti-inflammatory effects on the endothelium. In this study, we investigated the effects of memantine on human brain microvascular endothelial dysfunction induced by the pro-inflammatory cytokine tumor necrosis factor-α (TNF-α)...
April 20, 2017: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/28427672/current-status-and-future-perspectives-of-sonodynamic-therapy-in-glioma-treatment
#8
REVIEW
Xiaobing Wang, Yali Jia, Pan Wang, Quanhon Liu, Hairong Zheng
Malignant glioma is one of the most challenging central nervous system diseases to treat, and has high rates of recurrence and mortality. The current therapies include surgery, radiation therapy, and chemotherapy, although these approaches often failed to control tumor progression or improve patient survival. Sonodynamic therapy is a developing cancer treatment that uses ultrasound combined with a sonosensitizer to synergistically kill tumor cells, and has provided impressive results in both in vitro and in vivo studies...
July 2017: Ultrasonics Sonochemistry
https://www.readbyqxmd.com/read/28427013/the-accelerated-path-of-ceritinib-translating-pre-clinical-development-into-clinical-efficacy
#9
REVIEW
Tony S K Mok, Lucio Crino, Enriqueta Felip, Ravi Salgia, Tommaso De Pas, Daniel S W Tan, Laura Q M Chow
The discovery of anaplastic lymphoma kinase (ALK)-rearranged non-small-cell lung cancer (NSCLC) in 2007 led to the development and subsequent approval of the ALK inhibitor crizotinib in 2011. However, despite its clinical efficacy, resistance to crizotinib invariably develops. There is now a next generation of ALK inhibitors, including two that have been approved-ceritinib and alectinib-and others that are in development-brigatinib, lorlatinib and X-396. Ceritinib and the other next-generation ALK inhibitors are more potent than crizotinib and can overcome tumor cell resistance mechanisms...
March 30, 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28425046/mir-198-enhances-temozolomide-sensitivity-in-glioblastoma-by-targeting-mgmt
#10
Er Nie, Xin Jin, Weining Wu, Tianfu Yu, Xu Zhou, Zhumei Shi, Junxia Zhang, Ning Liu, Yongping You
Glioblastoma is one of the most frequent and aggressive brain tumors. Accumulating evidence indicates that microRNAs are involved in glioma proliferation, invasion and drug resistance. Previous studies showed that miR-198 is downregulated in glioblastoma. However, the function of miR-198 in glioblastoma is still unclear. In this study, we report that miR-198 levels were greatly downregulated in glioblastoma specimens and decreased expression of miR-198 was associated with poor prognosis in patients with glioblastoma...
April 19, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28422529/implant-compositions-for-the-unidirectional-delivery-of-drugs-to-the-brain
#11
Michael McGinity, John Floyd, James McGinity, Feng Zhang
The overall objective of this study was to design and characterize the properties of a bioadhesive trilayer sustained-release implant device for the unidirectional local delivery of anticancer compounds to the brain following the removal of glioblastoma multiforme tumors. Using acetaminophen as a model drug compound, we compressed trilayer wafers that contained (a) a bioadhesive layer, (b) a drug layer that contained a lipid and a pore-forming hydrophilic polymer, and (c) a third layer comprising a lipid substance...
April 19, 2017: Drug Development and Industrial Pharmacy
https://www.readbyqxmd.com/read/28421460/flow-arrest-intra-arterial-delivery-of-small-tat-decorated-and-neutral-micelles-to-gliomas
#12
Juliane Nguyen, Shaolie S Hossain, Johann R N Cooke, Jason A Ellis, Michael B Deci, Charles W Emala, Jeffrey N Bruce, Irving J Bigio, Robert M Straubinger, Shailendra Joshi
The cell-penetrating trans-activator of transcription (TAT) is a cationic peptide derived from human immunodeficiency virus-1. It has been used to facilitate macromolecule delivery to various cell types. This cationic peptide is capable of crossing the blood-brain barrier and therefore might be useful for enhancing the delivery of drugs that target brain tumors. Here we test the efficiency with which relatively small (20 nm) micelles can be delivered by an intra-arterial route specifically to gliomas. Utilizing the well-established method of flow-arrest intra-arterial injection we compared the degree of brain tumor deposition of cationic TAT-decorated micelles versus neutral micelles...
April 18, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28418861/brain-derived-neurotrophic-factor-involved-epigenetic-repression-of-ugt2b7-in-colorectal-carcinoma-a-mechanism-to-alter-morphine-glucuronidation-in-tumor
#13
Zi-Zhao Yang, Li Li, Ming-Cheng Xu, Hai-Xing Ju, Miao Hao, Jing-Kai Gu, Zai-Jie Jim Wang, Hui-Di Jiang, Lu-Shan Yu, Su Zeng
Uridine diphosphate-glucuronosyltransferase (UGT) 2B7, as one of significant drug enzymes, is responsible on the glucuronidation of abundant endobiotics or xenobiotics. We here report that it is markedly repressed in the tumor tissues of colorectal carcinoma (CRC) patients. Accordingly, morphine in CRC cells will stimulate the expression of its main metabolic enzyme, UGT2B7 during tolerance generation by activating the positive signals in histone 3, especially for trimethylated lysine 27 (H3K4Me3) and acetylated lysine 4 (H3K27Ac)...
March 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28418846/drug-carrying-microbubbles-as-a-theranostic-tool-in-convection-enhanced-delivery-for-brain-tumor-therapy
#14
Pin-Yuan Chen, Chih-Kuang Yeh, Po-Hung Hsu, Chung-Yin Lin, Chiung-Yin Huang, Kuo-Chen Wei, Hao-Li Liu
Convection-enhanced delivery (CED) is a promising technique for infusing a therapeutic agent through a catheter with a pressure gradient to create bulk flow for improving drug spread into the brain. So far, gadopentetate dimeglumine (Gd-DTPA) is the most commonly applied surrogate agent for predicting drug distribution through magnetic resonance imaging (MRI). However, Gd-DTPA provides only a short observation duration, and concurrent infusion provides an indirect measure of the exact drug distribution. In this study, we propose using microbubbles as a contrast agent for MRI monitoring, and evaluate their use as a drug-carrying vehicle to directly monitor the infused drug...
March 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28416781/incidence-risk-factors-and-outcomes-of-seizures-occurring-after-craniotomy-for-primary-brain-tumor-resection
#15
Hasan M Al-Dorzi, Abdullah A Alruwaita, Bothaina O Marae, Bushra S Alraddadi, Hani M Tamim, Ahmad Ferayan, Yaseen M Arabi
OBJECTIVE: To determine the incidence, risk factors and outcomes of early post-craniotomy seizures. METHODS: This was a retrospective cohort study of all patients who underwent craniotomy for primary brain tumor resection (2002-2011) and admitted postoperatively to the intensive care unit. The patients were divided into 2 groups depending on the occurrence of seizures within 7 days. RESULTS: One-hundred-ninety-three patients were studied: 35...
April 2017: Neurosciences: the Official Journal of the Pan Arab Union of Neurological Sciences
https://www.readbyqxmd.com/read/28412926/acute-symptomatic-seizures-in-geriatric-patients-with-multiple-risk-factors-a-diagnostic-challenge
#16
Ralf Landwehr, Robert Liszka
Acute symptomatic seizures and epileptic disorders are frequent health problems of elderly patients. An early and reliable distinction of the seizure etiology is important to ensure adequate treatment, and to prevent unwarranted diagnostic and therapeutic procedures. The most common causes of acute symptomatic seizures - acute cerebrovascular disorders, metabolic disorders, traumatic brain injury, meningo-encephalitis, cerebral tumors, and withdrawal of alcohol and other central agents - are well-defined and seem to permit straightforward diagnostic and therapeutic strategies...
April 13, 2017: Current Aging Science
https://www.readbyqxmd.com/read/28410530/metformin-attenuated-endotoxin-induced-acute-myocarditis-via-activating-ampk
#17
Gang Liu, Kejia Wu, Li Zhang, Jie Dai, Wei Huang, Ling Lin, Pu Ge, Fuling Luo, Han Lei
Metformin is a widely used anti-diabetic drug and increasing evidence suggests that metformin have profound cardioprotective effects under both diabetic and non-diabetic situations. The protective benefits of metformin have been proved in diabetic patients with cardiovascular complications and in experimental animals with myocardial infarction and cardiac hypertrophy. In the present study, we found that treatment with metformin inhibited the cardiac expression of pro-inflammatory cytokines including tumor necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1β) and interleukin 6 (IL-6) in endotoxin-challenged mice...
April 11, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28410232/vacquinol-1-inducible-cell-death-in-glioblastoma-multiforme-is-counter-regulated-by-trpm7-activity-induced-by-exogenous-atp
#18
Philip Sander, Haouraa Mostafa, Ayman Soboh, Julian M Schneider, Andrej Pala, Ann-Kathrin Baron, Barbara Moepps, C Rainer Wirtz, Michael Georgieff, E Marion Schneider
Glioblastomas (GBM) are the most malignant brain tumors in humans and have a very poor prognosis. New therapeutic options are urgently needed. A novel drug, Vacquinol-1 (Vac), a quinolone derivative, displays promising properties by inducing rapid cell death in GBM but not in non-transformed tissues. Features of this type of cell death are compatible with a process termed methuosis. Here we tested Vac on a highly malignant glioma cell line observed by long-term video microscopy. Human dental-pulp stem cells (DPSCs) served as controls...
March 30, 2017: Oncotarget
https://www.readbyqxmd.com/read/28409734/intratumoral-delivery-of-bortezomib-impact-on-survival-in-an-intracranial-glioma-tumor-model
#19
Weijun Wang, Hee-Yeon Cho, Rachel Rosenstein-Sisson, Nagore I Marín Ramos, Ryan Price, Kyle Hurth, Axel H Schönthal, Florence M Hofman, Thomas C Chen
OBJECTIVE Glioblastoma (GBM) is the most prevalent and the most aggressive of primary brain tumors. There is currently no effective treatment for this tumor. The proteasome inhibitor bortezomib is effective for a variety of tumors, but not for GBM. The authors' goal was to demonstrate that bortezomib can be effective in the orthotopic GBM murine model if the appropriate method of drug delivery is used. In this study the Alzet mini-osmotic pump was used to bring the drug directly to the tumor in the brain, circumventing the blood-brain barrier; thus making bortezomib an effective treatment for GBM...
April 14, 2017: Journal of Neurosurgery
https://www.readbyqxmd.com/read/28408882/targeted-nanotechnology-in-glioblastoma-multiforme
#20
REVIEW
Talita Glaser, Inbo Han, Liquan Wu, Xiang Zeng
Gliomas, and in particular glioblastoma multiforme, are aggressive brain tumors characterized by a poor prognosis and high rates of recurrence. Current treatment strategies are based on open surgery, chemotherapy (temozolomide) and radiotherapy. However, none of these treatments, alone or in combination, are considered effective in managing this devastating disease, resulting in a median survival time of less than 15 months. The efficiency of chemotherapy is mainly compromised by the blood-brain barrier (BBB) that selectively inhibits drugs from infiltrating into the tumor mass...
2017: Frontiers in Pharmacology
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