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https://www.readbyqxmd.com/read/28529554/novel-drugs-in-pediatric-gliomas
#1
Dongli Zhang, Xiaoming Liu, Conghai Fan, Jiao Chen
Astrocytomas (gliomas) are the most common primary brain tumors among adults and second most frequent neoplasm among children. New ideas and novel approaches are being explored world over with aim to devise better management strategeies for this deadly pathological state. We searched the electronic database PubMed for pre-clinical as well as clinical controlled trials reporting importance of various therapeutic drugs against gliomas. It was observed clearly that this approach of using therapeutic drugs is clearly evolving and has been observed to be promising future therapeutic avenue against gliomas...
May 2017: Oncology Letters
https://www.readbyqxmd.com/read/28528204/a-novel-pleiotropic-effect-of-aspirin-beneficial-regulation-of-pro-and-anti-inflammatory-mechanisms-in-microglial-cells
#2
Diana Kata, Imre Földesi, Liliana Z Feher, Laszlo Hackler, Laszlo G Puskas, Karoly Gulya
Aspirin, one of the most widely used non-steroidal anti-inflammatory drugs, has extensively studied effects on the cardiovascular system. To reveal further pleiotropic, beneficial effects of aspirin on a number of pro- and anti-inflammatory microglial mechanisms, we performed morphometric and functional studies relating to phagocytosis, pro- and anti-inflammatory cytokine production (IL-1β, tumor necrosis factor-α (TNF-α) and IL-10, respectively) and analyzed the expression of a number of inflammation-related genes, including those related to the above functions, in pure microglial cells...
May 17, 2017: Brain Research Bulletin
https://www.readbyqxmd.com/read/28528185/simvastatin-ameliorate-memory-deficits-and-inflammation-in-clinical-and-mouse-model-of-alzheimer-s-disease-via-modulating-the-expression-of-mir-106b
#3
Wenzhong Huang, Zhenyu Li, Liandong Zhao, Wei Zhao
BACKGROUND: Alzheimer's disease (AD) as a neurodegenerative brain disorder is a devastating pathology leading to disastrous cognitive impairments and dementia, and several studies have shown that AD is closely related to the inflammation, so anti-inflammatory treatment may provide therapeutic benefits. In this study, the effect of simvastatin on inflammation was investigated and the underlying mechanisms were explored. METHODS: First, we tested the effect of simvastatin on AD in clinical research...
May 18, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28527194/biodistribution-and-excretion-of-colloidal-gold-nanoparticles-after-intravenous-injection-effects-of-particle-size
#4
Issei Takeuchi, Sho Nobata, Naoto Oiri, Keishiro Tomoda, Kimiko Makino
BACKGROUND: Inorganic gold nanoparticles (NPs) have a huge potential in targeted drug delivery. Simple preparation and surface modification procedure with their special physicochemical properties of gold NPs attract their use such as tumor targeting and the detection of cancerous cell. OBJECTIVE: Various studies were reported, however, details of biodistribution profile of gold NPs were not enough evaluated. We have studied biodistribution profile of gold NPs having various particle sizes (20, 50 and 100 nm)...
2017: Bio-medical Materials and Engineering
https://www.readbyqxmd.com/read/28521703/recent-advances-in-antiepileptic-herbal-medicine
#5
Stephen M Manchishi
Epilepsy is one of the most common neurological disorders worldwide, with about 80 percent of cases thought to be in developing nations where it is mostly linked to superstition. Most cases of epilepsy are idiopathic, though brain injury, brain tumor, severe systemic infection and genetic mutations have been implicated in some cases. Anti-epileptic drugs (AEDs) currently in existence are not sufficient to contain the disorder. This is not only because of their limited availability and cost, but also their adverse side effects...
May 18, 2017: Current Neuropharmacology
https://www.readbyqxmd.com/read/28521298/insulin-like-growth-factor-2-axis-supports-the-serum-independent-growth-of-malignant-rhabdoid-tumor-and-is-activated-by-microenvironment-stress
#6
Ting Li, Jin Wang, Pengfei Liu, Jiadong Chi, Han Yan, Lei Lei, Zexing Li, Bing Yang, Xi Wang
Malignant rhabdoid tumors (MRTs) are rare, lethal, pediatric tumors predominantly found in the kidney, brain and soft tissues. MRTs are driven by loss of tumor suppressor SNF5/INI1/SMARCB1/BAF47. The prognosis of MRT is poor using currently available treatments, so new treatment targets need to be identified to expand treatment options for patients experiencing chemotherapy resistance. The growth hormone insulin-like growth factor 2 (IGF2) signaling pathway is a promising target to overcome drug resistance in many cancers...
May 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28513547/epigenetic-regulation-of-telomere-maintenance-for-therapeutic-interventions-in-gliomas
#7
REVIEW
Elisabeth Naderlinger, Klaus Holzmann
High-grade astrocytoma of WHO grade 4 termed glioblastoma multiforme (GBM) is a common human brain tumor with poor patient outcome. Astrocytoma demonstrates two known telomere maintenance mechanisms (TMMs) based on telomerase activity (TA) and on alternative lengthening of telomeres (ALT). ALT is associated with lower tumor grades and better outcome. In contrast to ALT, regulation of TA in tumors by direct mutation and epigenetic activation of the hTERT promoter is well established. Here, we summarize the genetic background of TMMs in non-malignant cells and in cancer, in addition to clinical and pathological features of gliomas...
May 17, 2017: Genes
https://www.readbyqxmd.com/read/28513420/optimization-of-glioblastoma-mouse-orthotopic-xenograft-models-for-translational-research
#8
Susan M Irtenkauf, Susan Sobiechowski, Laura A Hasselbach, Kevin K Nelson, Andrea D Transou, Enoch T Carlton, Tom Mikkelsen, Ana C deCarvalho
Glioblastoma is an aggressive primary brain tumor predominantly localized to the cerebral cortex. We developed a panelofpatient-derived mouse orthotopic xenografts (PDOX) for preclinical drug studies by implanting cancer stem cells (CSC) cultured from fresh surgical specimens intracranially into 8-wk-old female athymic nude mice. Here we optimize the glioblastoma PDOX model by assessing the effect of implantation location on tumor growth, survival, and histologic characteristics. To trace the distribution of intracranial injections, toluidine blue dye was injected at 4 locations with defined mediolateral, anterioposterior, and dorsoventral coordinates within the cerebral cortex...
May 16, 2017: Comparative Medicine
https://www.readbyqxmd.com/read/28512255/immune-consequences-of-penfluridol-treatment-associated-with-inhibition-of-glioblastoma-tumor-growth
#9
Alok Ranjan, Stephen Wright, Sanjay K Srivastava
Glioblastoma is the most common and lethal brain tumor associated with only 12% median survival rate of patients. Despite the development of advanced surgical, radiation or use of combinations of anti-cancer drugs, treatment for glioblastoma patients is still a challenge. The major contributing factor in glioblastoma progression and resistive nature is its ability to evade the immune surveillance. Hence, modulating the immune system in glioblastoma tumors could be an important strategy for anticancer therapeutics...
April 26, 2017: Oncotarget
https://www.readbyqxmd.com/read/28512108/clinical-relevance-and-role-of-neuronal-at1-receptors-in-adam17-mediated-ace2-shedding-in-neurogenic-hypertension
#10
Jiaxi Xu, Srinivas Sriramula, Huijing Xia, Lisa Moreno-Walton, Frank Culicchia, Oliver Domenig, Marko Poglitsch, Eric Lazartigues
Rationale: Neurogenic hypertension is characterized by an increase in sympathetic activity and often resistance to drug treatments. We previously reported that it is also associated with a reduction of Angiotensin Converting Enzyme 2 (ACE2) and an increase in A Disintegrin And Metalloprotease 17 (ADAM17) activity in experimental hypertension. In addition, while multiple cells within the central nervous system have been involved in the development of neurogenic hypertension, the contribution of ADAM17 has not been investigated...
May 16, 2017: Circulation Research
https://www.readbyqxmd.com/read/28510992/lymph-node-effective-vascular-permeability-and-chemotherapy-uptake
#11
Eelco Fj Meijer, Cedric Blatter, Ivy X Chen, Echoe Bouta, Dennis Jones, Ethel R Pereira, Keehoon Jung, Benjamin J Vakoc, James W Baish, Timothy P Padera
OBJECTIVE: Lymph node metastases are a poor prognostic factor. Additionally, responses of lymph node metastasis to therapy can be different from the primary tumor. Investigating the physiologic lymph node blood vasculature might give insight into the ability of systemic drugs to penetrate the lymph node, and thus into the differential effect of therapy between lymph node metastasis and primary tumors. Here, we measured effective vascular permeability of lymph node blood vessels and attempted to increase chemotherapy penetration by increasing effective vascular permeability...
May 16, 2017: Microcirculation: the Official Journal of the Microcirculatory Society, Inc
https://www.readbyqxmd.com/read/28508321/trpc-channels-and-glioma
#12
Shanshan Li, Xia Ding
Glioma is the most common type of brain tumors and malignant glioma is extremely lethal, with patients' 5-year survival rate less than 10%. Treatment of gliomas poses remarkable clinical challenges, not only because of their particular localization but also because glioma cells possess several malignant biological features, including highly proliferative, highly invasive, highly angiogenic, and highly metabolic aberrant. All these features make gliomas highly recurrent and drug resistant. Finding new and effective molecular drug targets for glioma is an urgent and critical task for both basic and clinical research...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28504687/the-kinesin-kif14-is-overexpressed-in-medulloblastoma-and-downregulation-of-kif14-suppressed-tumor-proliferation-and-induced-apoptosis
#13
Kay Ka-Wai Li, Yan Qi, Tian Xia, Aden Ka-Yin Chan, Zhen-Yu Zhang, Abudumijiti Aibaidula, Rong Zhang, Liangfu Zhou, Yu Yao, Ho-Keung Ng
Medulloblastoma (MB) is the most common malignant brain tumor in childhood. At present, there is no well-established targeted drug for majority of patients. The kinesin family member 14 (KIF14) is a novel oncogene located on chromosome 1q and is dysregulated in multiple cancers. The objectives of this study were to evaluate KIF14 expression and chromosome 1q copy number in MB, and to delineate its biological functions in MB pathogenesis. By quantitative RT-PCR and immunohistochemistry, we found KIF14 was overexpressed in MB...
May 15, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28502470/antitumoral-cascade-targeting-ligand-for-il-6-receptor-mediated-gene-delivery-to-glioma
#14
Shanshan Wang, Sören Reinhard, Chengyi Li, Min Qian, Huiling Jiang, Yilin Du, Ulrich Lächelt, Weiyue Lu, Ernst Wagner, Rongqin Huang
The effective treatment of glioma is largely hindered by the poor transfer of drug delivery systems across the blood-brain barrier (BBB) and the difficulty in distinguishing healthy and tumorous cells. In this work, for the first time, an interleukin-6 receptor binding I6P7 peptide was exploited as a cascade-targeting ligand in combination with a succinoyl tetraethylene pentamine (Stp)-histidine oligomer-based nonviral gene delivery system (I6P7-Stp-His/DNA). The I6P7 peptide provides multiple functions, including the cascade-targeting potential represented by a combined BBB-crossing and subsequent glioma-targeting ability, as well as a direct tumor-inhibiting effect...
May 10, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28500786/dovitinib-enhances-temozolomide-efficacy-in-glioblastoma-cells
#15
Thatchawan Thanasupawat, Suchitra Natarajan, Amy Rommel, Aleksandra Glogowska, Hugo Bergen, Jerry Krcek, Marshall Pitz, Jason Beiko, Sherry Krawitz, Inder M Verma, Saeid Ghavami, Thomas Klonisch, Sabine Hombach-Klonisch
The multikinase inhibitor and FDA-approved drug Dovitinib (Dov) crosses the blood-brain-barrier and was recently used as single drug application in clinical trials for GB patients with recurrent disease. The Dov-mediated molecular mechanisms in GB cells are unknown. We used GB patient cells and cell lines to show that Dov downregulated the stem cell protein Lin28 and its target High Mobility Group protein A2 (HMGA2). The Dov-induced reduction in pSTAT3(Tyr705) phosphorylation demonstrated that Dov negatively affects the STAT3-LIN28-Let-7-HMGA2 regulatory axis in GB cells...
May 13, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28499974/prefrontal-cortical-glutathione-dependent-defense-and-proinflammatory-mediators-in-chronically-isolated-rats-modulation-by-fluoxetine-or-clozapine
#16
Nevena Todorović, Dragana Filipović
Chronic psychosocial stress modulates brain antioxidant systems and causes neuroinflammation that plays a role in the pathophysiology of depression. Although the antidepressant fluoxetine (FLX) represents the first-line treatment for depression and the atypical antipsychotic clozapine (CLZ) is considered as a second-line treatment for psychotic disorders, the downstream mechanisms of action of these treatments, beyond serotonergic or dopaminergic signaling, remain elusive. We examined behavioral changes, glutathione (GSH)-dependent defense and levels of proinflammatory mediators in the prefrontal cortex (PFC) of adult male Wistar rats exposed to 21days of chronic social isolation (CSIS)...
May 10, 2017: Neuroscience
https://www.readbyqxmd.com/read/28498936/a-phase-1-dose-escalation-study-of-oral-5-aminolevulinic-acid-in-adult-patients-undergoing-resection-of-a-newly-diagnosed-or-recurrent-high-grade-glioma
#17
Jeffrey W Cozzens, Barbara C Lokaitis, Brian E Moore, Devin V Amin, José A Espinosa, Margaret MacGregor, Alex P Michael, Breck A Jones
BACKGROUND: The utility of oral 5-aminolevulinic acid (5-ALA)/protoporphyrin fluorescence for the resection of high-grade gliomas is well documented. This drug has received regulatory approval in Europe but awaits approval in the United States. OBJECTIVE: To identify the appropriate dose and toxicity or harms of 5-ALA used for enhanced intraoperative visualization of malignant brain tumors, reported from a single medical center in the United States. METHODS: Prior to craniotomy for resection of a presumed high-grade glioma, individuals were given oral 5-ALA as part of a rapid dose-escalation scheme...
May 10, 2017: Neurosurgery
https://www.readbyqxmd.com/read/28497694/stapled-rgd-peptide-enables-glioma-targeted-drug-delivery-by-overcoming-multiple-barriers
#18
Huitong Ruan, Xishan Chen, Cao Xie, Beibei Li, Man Ying, Yu Liu, Mingfei Zhang, Xuesai Zhang, Changyou Zhan, Wuyuan Lu, Weiyue Lu
Malignant glioma, the most frequent and aggressive central nervous system (CNS) tumor, severely threatens human health. One reason for its poor prognosis and short survival is the presence of the blood-brain barrier (BBB) and blood-brain tumor barrier (BBTB), which restrict the penetration of therapeutics into the brain at different stages of glioma. Herein, inspired by the peptide stapling technique, we designed a cyclic RGD ligand via an all-hydrocarbon staple (stapled RGD, sRGD) to facilitate BBB penetration while retaining the capacity of BBTB penetration and targeting ability to glioma cells...
May 18, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28497109/hippocampal-tnf%C3%AE-signaling-contributes-to-seizure-generation-in-an-infection-induced-mouse-model-of-limbic-epilepsy
#19
Dipan C Patel, Glenna Wallis, E Jill Dahle, Pallavi B McElroy, Kyle E Thomson, Raymond J Tesi, David E Szymkowski, Peter J West, Roy M Smeal, Manisha Patel, Robert S Fujinami, H Steve White, Karen S Wilcox
Central nervous system infection can induce epilepsy that is often refractory to established antiseizure drugs. Previous studies in the Theiler's murine encephalomyelitis virus (TMEV)-induced mouse model of limbic epilepsy have demonstrated the importance of inflammation, especially that mediated by tumor necrosis factor-α (TNFα), in the development of acute seizures. TNFα modulates glutamate receptor trafficking via TNF receptor 1 (TNFR1) to cause increased excitatory synaptic transmission. Therefore, we hypothesized that an increase in TNFα signaling after TMEV infection might contribute to acute seizures...
March 2017: ENeuro
https://www.readbyqxmd.com/read/28490320/astaxanthin-protects-astrocytes-against-trauma-induced-apoptosis-through-inhibition-of-nkcc1-expression-via-the-nf-%C3%AE%C2%BAb-signaling-pathway
#20
Mingkun Zhang, Zhenwen Cui, Hua Cui, Yong Wang, Chunlong Zhong
BACKGROUND: Astaxanthin (ATX) is a carotenoid pigment with pleiotropic pharmacological properties that is seen as a possible drug for treating cerebral ischemic injury and subarachnoid hemorrhage. Na(+)-K(+)-2Cl(-) co-transporter-1 (NKCC1), an intrinsic membrane protein expressed by many cell types, is activated by various insults, leading to the formation of cell swelling and brain edema. We previously established that ATX attenuated brain edema and improved neurological outcomes by modulating NKCC1 expression after traumatic brain injury in mice...
May 10, 2017: BMC Neuroscience
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