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https://www.readbyqxmd.com/read/28731079/a-polymeric-temozolomide-nanocomposite-against-orthotopic-glioblastoma-xenograft-tumor-specific-homing-directed-by-nestin
#1
Suma Prabhu, Jayant Sastri Goda, Srinivas Mutalik, Bhabani Shankar Mohanty, Pradip Chaudhari, Sharada Rai, Nayanabhirama Udupa, Bola Sadashiva Satish Rao
The development of effective therapeutic strategies for glioblastoma faces challenges such as modulating the blood brain barrier (BBB) for drug influx and selectively targeting tumor cells. Nanocarrier drug delivery strategies are functionalized to enhance vascular permeability. We engineered superparamagnetic iron oxide nanoparticle (SPION) based polymeric nanocomposites (84.37 ± 12.37 nm / 101.56 ± 7.42 nm) embedding temozolomide (TMZ) targeted against glioblastoma by tagging an antibody against nestin, a stem cell marker, and transferrin / polysorbate-80 to permeate the BBB...
July 21, 2017: Nanoscale
https://www.readbyqxmd.com/read/28726961/functional-single-walled-carbon-nanotubes-car-for-targeting-dopamine-delivery-into-the-brain-of-parkinsonian-mice
#2
Qing Guo, Huihui You, Xu Yang, Bencheng Lin, Zhihong Zhu, Zhisong Lu, Xiaoxiao Li, Yun Zhao, Lin Mao, Shiping Shen, Haoyan Cheng, Jiting Zhang, Lingfu Deng, Jianhua Fan, Zhuge Xi, Rui Li, Chang Ming Li
Current treatments for Parkinson's disease (PD) are limited, partly due to the difficulties posed by the blood brain barrier (BBB) when delivering drugs to the brain. Herein, we explore the feasibility and efficacy of functional single-walled carbon nanotubes 'CAR' (SWCNT-PEGs-Lf) which carry and target-deliver dopamine (DA) to the brain in PD mice for treatment. SWCNTs can penetrate the cell-membrane remarkably, with the characteristics including high drug-loading and pH-dependent therapeutic unloading capacities...
July 20, 2017: Nanoscale
https://www.readbyqxmd.com/read/28725965/medulloblastoma-experimental-models-and-reality
#3
REVIEW
Julia E Neumann, Fredrik J Swartling, Ulrich Schüller
Medulloblastoma is the most frequent malignant brain tumor in childhood, but it may also affect infants, adolescents, and young adults. Recent advances in the understanding of the disease have shed light on molecular and clinical heterogeneity, which is now reflected in the updated WHO classification of brain tumors. At the same time, it is well accepted that preclinical research and clinical trials have to be subgroup-specific. Hence, valid models have to be generated specifically for every medulloblastoma subgroup to properly mimic molecular fingerprints, clinical features, and responsiveness to targeted therapies...
July 19, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28719459/coagulation-management-in-patients-undergoing-neurosurgical-procedures
#4
Chiara Robba, Rita Bertuetti, Frank Rasulo, Alessando Bertuccio, Basil Matta
PURPOSE OF REVIEW: Management of coagulation in neurosurgical procedures is challenging. In this contest, it is imperative to avoid further intracranial bleeding. Perioperative bleeding can be associated with a number of factors, including anticoagulant drugs and coagulation status but is also linked to the characteristic and the site of the intracranial disorder. The aim of this review will be to focus primarily on the new evidence regarding the management of coagulation in patients undergoing craniotomy for neurosurgical procedures...
July 14, 2017: Current Opinion in Anaesthesiology
https://www.readbyqxmd.com/read/28718326/cns-anticancer-drug-discovery-and-development-2016-conference-insights
#5
Victor A Levin, Lauren E Abrey, Timothy P Heffron, Peter J Tonge, Arvin C Dar, William A Weiss, James M Gallo
CNS Anticancer Drug Discovery and Development November 2016, AZ, USA The 2016 second CNS Anticancer Drug Discovery and Development Conference addressed diverse viewpoints about why new drug discovery/development focused on CNS cancers has been sorely lacking. Despite more than 70,000 individuals in the USA being diagnosed with a primary brain malignancy and 151,669-286,486 suffering from metastatic CNS cancer, in 1999, temozolomide was the last drug approved by the US FDA as an anticancer agent for high-grade gliomas...
July 18, 2017: CNS Oncology
https://www.readbyqxmd.com/read/28716053/ibrutinib-a-bruton-s-tyrosine-kinase-inhibitor-exhibits-antitumoral-activity-and-induces-autophagy-in-glioblastoma
#6
Jin Wang, Xiaoyang Liu, Yongzhi Hong, Songtao Wang, Pin Chen, Aihua Gu, Xiaoyuan Guo, Peng Zhao
BACKGROUND: Glioblastoma (GBM) is the most common and aggressive primary brain tumor in adults. Ibrutinib, a Bruton's tyrosine kinase (BTK) inhibitor, is a novel anticancer drug used for treating several types of cancers. In this study, we aimed to determine the role of ibrutinib on GBM. METHODS: Cell proliferation was determined by using cell viability, colony formation, and 5-ethynyl-2'-deoxyuridine (EdU) assays. Cell cycle and cell apoptosis were analyzed by flow cytometry...
July 17, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28715490/patterns-of-care-of-brain-tumor-related-epilepsy-a-cohort-study-done-in-italian-epilepsy-center
#7
Marta Maschio, Ettore Beghi, Marina M L Casazza, Gabriella Colicchio, Cinzia Costa, Paola Banfi, Stefano Quadri, Paolo Aloisi, Anna Teresa Giallonardo, Carla Buttinelli, Giada Pauletto, Salvatore Striano, Andrea Salmaggi, Riccardo Terenzi, Ornella Daniele, Giovanni Crichiutti, Francesco Paladin, Rosario Rossi, Giulia Prato, Federico Vigevano, Roberto De Simone, Federica Ricci, Marina Saladini, Fabrizio Monti, Susanna Casellato, Tiziano Zanoni, Diana Giannarelli, Giuliano Avanzini, Umberto Aguglia
Epilepsy is the most common comorbidity in patients with brain tumors. STUDY AIMS: To define characteristics of brain tumor-related epilepsy (BTRE) patients and identify patterns of care. Nationwide, multicenter retrospective cohort study. Medical records of BTRE patients seen from 1/1/2010 to 12/31/2011, followed for at least one month were examined. Information included age, sex, tumor type/treatments, epilepsy characteristics, antiepileptic drugs (AEDs). Time to modify first AED due to inefficacy and/or toxicity was assessed with the Kaplan-Meier method and Cox proportional hazard models were used to identify predictors of treatment outcome...
2017: PloS One
https://www.readbyqxmd.com/read/28713881/drug-delivery-and-nanoformulations-for-the-cardiovascular-system
#8
W J Geldenhuys, M T Khayat, J Yun, M A Nayeem
Therapeutic delivery to the cardiovascular system may play an important role in the successful treatment of a variety of disease state, including atherosclerosis, ischemic-reperfusion injury and other types of microvascular diseases including hypertension. In this review we evaluate the different options available for the development of suitable delivery systems that include the delivery of small organic compounds [adenosin A2A receptor agonist (CGS 21680), CYP-epoxygenases inhibitor (N-(methylsulfonyl)-2-(2-propynyloxy)-benzenehexanamide, trans-4-[4-(3-adamantan-1-ylureido)cyclohexyloxy] benzoic acid), soluble epoxide hydrolase inhibitor (N-methylsulfonyl-12,12-dibromododec-11-enamide), PPARγ agonist (rosiglitazone) and PPARγ antagonist (T0070907)], nanoparticles, peptides, and siRNA to the cardiovascular system...
February 2017: Res Rev Drug Deliv
https://www.readbyqxmd.com/read/28713152/metastatic-anaplastic-lymphoma-kinase-1-alk-1-rearranged-inflammatory-myofibroblastic-sarcoma-to-the-brain-with-leptomeningeal-involvement-favorable-response-to-serial-alk-inhibitors-a-case-report
#9
Cai Yuan, Muchou J Ma, John V Parker, Tarek M Mekhail
BACKGROUND ALK gene rearrangements as oncogenic drivers have been described in many cancers, including inflammatory myofibroblastic sarcoma (IMS). The first-generation ALK inhibitor was limited in its ability to cross the blood-brain-barrier to treat brain metastasis. Drug-resistance invariably develops over time in ALK-rearranged tumors, which leads to disease progression. The newer generations of ALK inhibitors are designed to have higher potency in ALK inhibition and improved CNS penetration. CASE REPORT We report a rare case of pulmonary IMS with ALK-1 gene rearrangement and multiple brain metastases as initial presentation...
July 17, 2017: American Journal of Case Reports
https://www.readbyqxmd.com/read/28712306/targeting-intrinsic-apoptosis-and-other-forms-of-cell-death-by-bh3-mimetics-in-glioblastoma
#10
Georg Karpel-Massler, Chiaki Tsuge Ishida, Yiru Zhang, Marc-Eric Halatsch, M-Andrew Westhoff, Markus D Siegelin
Novel approaches to treat malignant brain tumors are necessary since these neoplasms still display an unfavorable prognosis. Areas covered: In this review, the authors summarize and analyze recent preclinical data that suggest that targeting intrinsic apoptosis may be a suitable strategy for the treatment of malignant gliomas. They focus on the anti-apoptotic Bcl-2 family members of proteins and the recent drug developments in that field with a special focus on BH3-mimetics. With the discovery of BH3-mimetics that interfere with anti-apoptotic Bcl-2 family members in the low nanomolar range significant excitement has been generated towards these class of inhibitors, such as ABT-737, ABT-263 and the most recent successor, ABT-199 which is most advanced with respect to clinical application...
July 17, 2017: Expert Opinion on Drug Discovery
https://www.readbyqxmd.com/read/28710334/stem-cell-released-oncolytic-herpes-simplex-virus-has-therapeutic-efficacy-in-brain-metastatic-melanomas
#11
Wanlu Du, Ivan Seah, Oumaima Bougazzoul, GiHun Choi, Katrina Meeth, Marcus W Bosenberg, Hiroaki Wakimoto, David Fisher, Khalid Shah
The recent Food and Drug Administration approval of immunogenic oncolytic virus (OV) has opened a new era in the treatment of advanced melanoma; however, approximately 50% of patients with melanoma develop brain metastasis, and currently there are no beneficial treatment options for such patients. To model the progression of metastases seen in patients and to overcome the hurdles of systemic delivery of OV, we developed melanoma brain metastasis models in immunocompromised and immunocompetent mice, and tested the fate and efficacy of oncolytic herpes simplex virus (oHSV)-armed mesenchymal stem cells (MSCs)...
July 14, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28706504/hypertrophic-olivary-degeneration-and-palatal-or-oculopalatal-tremor
#12
REVIEW
Caroline Tilikete, Virginie Desestret
Hypertrophic degeneration of the inferior olive is mainly observed in patients developing palatal tremor (PT) or oculopalatal tremor (OPT). This syndrome manifests as a synchronous tremor of the palate (PT) and/or eyes (OPT) that may also involve other muscles from the branchial arches. It is associated with hypertrophic inferior olivary degeneration that is characterized by enlarged and vacuolated neurons, increased number and size of astrocytes, severe fibrillary gliosis, and demyelination. It appears on MRI as an increased T2/FLAIR signal intensity and enlargement of the inferior olive...
2017: Frontiers in Neurology
https://www.readbyqxmd.com/read/28700334/anti-sstr2-peptide-based-targeted-delivery-of-potent-plga-encapsulated-3-3%C3%A2-diindolylmethane-nanoparticles-through-blood-brain-barrier-prevents-glioma-progression
#13
Stelitano Debora, Peche Leticia Yamila, Dalla Emiliano, Monte Martin, Piazza Silvano, Schneider Claudio
GTSE1 over-expression has been reported as a potential marker for metastasis in various types of malignancies, including breast cancer. Despite this, the transcriptional regulation of this protein and the causes of its misregulation in tumors remain largely unknown. The aims of this work were to elucidate how GTSE1 is regulated at the transcriptional level and to clarify the mechanism underlying GTSE1-dependent cell functions in triple-negative breast cancer (TNBC).Here, we identified GTSE1 as a novel target gene of the TEAD4 transcription factor, highlighting a role for the YAP and TAZ coactivators in the transcriptional regulation of GTSE1...
June 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28699529/targeting-protein-kinases-for-the-treatment-of-glioblastoma-multiforme-linking-basic-studies-to-clinical-applications
#14
Aidong Zhou
Glioblastoma multiforme (GBM) is the most common malignant primary brain tumor in adults with intensive heterogeneity and one of the most lethal human cancers. Protein kinases control diverse cellular processes by coordinating different signaling pathways. Protein kinases are frequently dysregulated in human cancers, which contributes to tumor initiation and development. Thus, protein kinases are a growing drug target class for cancers including glioblastoma. This review focuses on the most important protein kinases and kinase-mediated signaling cascades in glioblastoma, and discusses the functional mechanism of these kinases in glioblastoma tumorigenesis...
July 10, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28696243/inhibiting-4ebp1-in-glioblastoma
#15
Qi Wen Fan, Theodore P Nicolaides, William A Weiss
Glioblastoma is the most common and aggressive adult brain cancer. Tumors show frequent dysregulation of the phosphatidylinositol-3 kinase-mechanistic target of rapamycin pathway. While a number of small molecules target the PI3K-AKT-mTOR axis, their preclinical and clinical efficacy has been limited. Reasons for treatment failure include poor penetration of agents into the brain, and observations that blockade of PI3K or AKT minimally affects downstream mTOR activity in glioma. Clinical trials using allosteric mTOR inhibitors (rapamycin and rapalogs) to treat glioblastoma patients have also been unsuccessful or uncertain, in-part because rapamycin inefficiently blocks the mTORC1 target 4EBP1, and also feeds back to activate PI3K-AKT signaling...
July 10, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28695794/the-natural-component-isolated-from-enterolobium-contortisiliquum-impairs-brain-tumors-and-affects-their-interactions-with-mesenchymal-stem-cells
#16
Camila Ramalho Bonturi, Helena Motaln, Mariana Cristina Cabral Silva, Bruno Ramos Salu, Marlon Vilela de Brito, Luciana de Andrade Luz Costa, Heron Fernandes Vieira Torquato, Natália Neto Dos Santos Nunes, Edgar Julian Paredes-Gamero, Tamara Lah Turnšek, Maria Luiza Vilela Oliva
Glioblastoma multiforme (GBM) is the most aggressive type of brain tumor with an overall patient survival of about 16 months. Thus, natural compounds with anti-cancer properties are gaining attention as possible alternatives for GBM treatment. Studies in various cancer models have shown the anti-cancer effects of the Enterolobium contortisiliquum Trypsin Inhibitor (EcTI). Here, we investigated the outcomes of EcTI on U87 cells, mesenchymal stem cells (MSC), and their direct cocultures (U87/MSC). MSC are present in tumor stroma and represent a potential drug delivery vehicle as the result of their tumor tropism...
July 11, 2017: Oncology Research
https://www.readbyqxmd.com/read/28693158/relationship-between-mgmt-gene-expression-and-treatment-effectiveness-and-prognosis-in-glioma
#17
Qiang Li, Jiang Guo, Weisheng Wang, Dingkun Wang
The expression of O(6)-methylguanine DNA methyltransferase (MGMT) in different grade gliomas were analyzed in relation to its therapeutic effect and impact on disease prognosis. In total, 62 patients with glioma, who were admitted by neurosurgery and received surgical treatment and postoperative conventional chemoradiation, were selected for this study. Expression of MGMT was greater with an increase in brain glioma grade. Gender, age, tumor size and Karnofsky performance status (KPS) score did not differ with MGMT expression (P>0...
July 2017: Oncology Letters
https://www.readbyqxmd.com/read/28687044/dual-modified-liposome-codelivery-of-doxorubicin-and-vincristine-improve-targeting-and-therapeutic-efficacy-of-glioma
#18
Yue Zhang, Meifang Zhai, Zhijiang Chen, Xiaoyang Han, Fanglin Yu, Zhiping Li, Xiangyang Xie, Cuiyan Han, Lian Yu, Yang Yang, Xingguo Mei
Therapeutic outcome for the treatment of glioma was often limited due to drug resistance and low permeability of drug across the multiple physiological barriers, including the blood-brain barrier (BBB), and the blood-tumor barrier (BTB). In order to overcome these hurdles, we designed T7 and (D)A7R dual peptides-modified liposomes (abbreviated as T7/(D)A7R-LS) to efficiently co-delivery doxorubicin (DOX) and vincristine (VCR) to glioma in this study. T7 is a seven-peptide ligand of transferrin receptors (TfR) capable of circumventing the BBB and then targeting glioma...
November 2017: Drug Delivery
https://www.readbyqxmd.com/read/28685422/chronic-diseases-as-barriers-to-oxygen-delivery-a-unifying-hypothesis-of-tissue-reoxygenation-therapy
#19
G A Perdrizet
Modern medical practice has resulted in the accumulation of a growing number of incurable chronic diseases, many of which are inflammatory in nature. Inflammation establishes a hypoxic microenvironment within tissues, a condition of inflammatory hypoxia (IH). Tissues thus affected become severely compromised, are unable to elicit adaptive responses and eventually develop fibrosis and fixed microvascular deficits. Previous work has demonstrated that tissue hypoxia exits even within the simple human model of self-resolving inflammation, the tuberculin reaction...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28684169/a-potential-non-invasive-glioblastoma-treatment-nose-to-brain-delivery-of-farnesylthiosalicylic-acid-incorporated-hybrid-nanoparticles
#20
Emine Sekerdag, Sevda Lüle, Sibel Bozdağ Pehlivan, Naile Öztürk, Aslı Kara, Abbas Kaffashi, Imran Vural, Ilkay Işıkay, Burҫin Yavuz, Kader Karlı Oguz, Figen Söylemezoğlu, Yasemin Gürsoy-Özdemir, Melike Mut
New drug delivery systems are highly needed in research and clinical area to effectively treat gliomas by reaching a high antineoplastic drug concentration at the target site without damaging healthy tissues. Intranasal (IN) administration, an alternative route for non-invasive drug delivery to the brain, bypasses the blood-brain-barrier (BBB) and eliminates systemic side effects. This study evaluated the antitumor efficacy of farnesylthiosalicylic acid (FTA) loaded (lipid-cationic) lipid-PEG-PLGA hybrid nanoparticles (HNPs) after IN application in rats...
July 3, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
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