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Convection-enhanced delivery

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https://www.readbyqxmd.com/read/29198324/developing-chemotherapy-for-diffuse-pontine-intrinsic-gliomas-dipg
#1
REVIEW
Ho-Shin Gwak, Hyeon Jin Park
Prognosis of diffuse intrinsic pontine glioma (DIPG) is poor, with a median survival of 10 months after radiation. At present, chemotherapy has failed to show benefits over radiation. Advances in biotechnology have enabled the use of autopsy specimens for genomic analyses and molecular profiling of DIPG, which are quite different from those of supratentorial high grade glioma. Recently, combined treatments of cytotoxic agents with target inhibitors, based on biopsied tissue, are being examined in on-going trials...
December 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/29170909/new-therapeutic-approaches-for-brainstem-tumors-a-comparison-of-delivery-routes-using-nanoliposomal-irinotecan-in-an-animal-model
#2
Nundia Louis, Sharon Liu, Xingyao He, Daryl C Drummond, Charles O Noble, Stewart Goldman, Sabine Mueller, Krystof Bankiewicz, Nalin Gupta, Rintaro Hashizume
Despite the advances in imaging, surgery and radiotherapy, the majority of patients with brainstem gliomas die within 2 years after initial diagnosis. Factors that contribute to the dismal prognosis of these patients include the infiltrative nature and anatomic location in an eloquent area of the brain, which prevents total surgical resection and the presence of the blood-brain barrier (BBB), which reduces the distribution of systemically administered agents. The development of new therapeutic approaches which can circumvent the BBB is a potential path to improve outcomes for these children...
November 23, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/29164054/effective-drug-delivery-in-diffuse-intrinsic-pontine-glioma-a-theoretical-model-to-identify-potential-candidates
#3
Fatma E El-Khouly, Dannis G van Vuurden, Thom Stroink, Esther Hulleman, Gertjan J L Kaspers, N Harry Hendrikse, Sophie E M Veldhuijzen van Zanten
Despite decades of clinical trials for diffuse intrinsic pontine glioma (DIPG), patient survival does not exceed 10% at two years post-diagnosis. Lack of benefit from systemic chemotherapy may be attributed to an intact bloodbrain barrier (BBB). We aim to develop a theoretical model including relevant physicochemical properties in order to review whether applied chemotherapeutics are suitable for passive diffusion through an intact BBB or whether local administration via convection-enhanced delivery (CED) may increase their therapeutic potential...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/29158842/locoregional-confinement-and-major-clinical-benefit-of-188-re-loaded-cxcr4-targeted-nanocarriers-in-an-orthotopic-human-to-mouse-model-of-glioblastoma
#4
Delphine Séhédic, Igor Chourpa, Clément Tétaud, Audrey Griveau, Claire Loussouarn, Sylvie Avril, Claire Legendre, Nicolas Lepareur, Didier Wion, François Hindré, François Davodeau, Emmanuel Garcion
PURPOSE: Gold standard beam radiation for glioblastoma (GBM) treatment is challenged by resistance phenomena occurring in cellular populations well prepared to survive or to repair damage caused by radiation. Among signals that have been linked with radio-resistance, the SDF1/CXCR4 axis, associated with cancer stem-like cell, may be an opportune target. To avoid the problem of systemic toxicity and blood-brain barrier crossing, the relevance and efficacy of an original system of local brain internal radiation therapy combining a radiopharmaceutical with an immuno-nanoparticle was investigated...
2017: Theranostics
https://www.readbyqxmd.com/read/29151166/t2-weighted-images-are-superior-to-other-mr-image-types-for-the-determination-of-diffuse-intrinsic-pontine-glioma-intratumoral-heterogeneity
#5
Stephen Harward, S Harrison Farber, Michael Malinzak, Oren Becher, Eric M Thompson
PURPOSE: Diffuse intrinsic pontine glioma (DIPG) remains the main cause of death in children with brain tumors. Given the inefficacy of numerous peripherally delivered agents to treat DIPG, convection enhanced delivery (CED) of therapeutic agents is a promising treatment modality. The purpose of this study was to determine which MR imaging type provides the best discrimination of intratumoral heterogeneity to guide future stereotactic implantation of CED catheters into the most cellular tumor regions...
November 18, 2017: Child's Nervous System: ChNS: Official Journal of the International Society for Pediatric Neurosurgery
https://www.readbyqxmd.com/read/29123246/transport-of-drugs-from-blood-vessels-to-tumour-tissue
#6
REVIEW
Mark W Dewhirst, Timothy W Secomb
The effectiveness of anticancer drugs in treating a solid tumour is dependent on delivery of the drug to virtually all cancer cells in the tumour. The distribution of drug in tumour tissue depends on the plasma pharmacokinetics, the structure and function of the tumour vasculature and the transport properties of the drug as it moves through microvessel walls and in the extravascular tissue. The aim of this Review is to provide a broad, balanced perspective on the current understanding of drug transport to tumour cells and on the progress in developing methods to enhance drug delivery...
November 10, 2017: Nature Reviews. Cancer
https://www.readbyqxmd.com/read/29081990/a-model-for-optimizing-delivery-of-targeted-radionuclide-therapies-into-resection-cavity-margins-for-the-treatment-of-primary-brain-cancers
#7
Raghu Raghavan, Roger W Howell, Michael R Zalutsky
Radionuclides conjugated to molecules that bind specifically to cancer cells are of great interest as a means to increase the specificity of radiotherapy. Currently, the methods to disseminate these targeted radiotherapeutics have been either systemic delivery or by bolus injection into the tumor or tumor resection cavity. Herein we model a potentially more efficient method of delivery, namely pressure-driven fluid flow, called convection-enhanced delivery (CED), where a device infuses the molecules in solution (or suspension) directly into the tissue of interest...
June 2017: Biomedical Physics & Engineering Express
https://www.readbyqxmd.com/read/29042259/widespread-optogenetic-expression-in-macaque-cortex-obtained-with-mr-guided-convection-enhanced-delivery-ced-of-aav-vector-to-the-thalamus
#8
Azadeh Yazdan-Shahmorad, Nan Tian, Viktor Kharazia, Lluis Samaranch, Adrian Kells, John Bringas, Jiwei He, Krystof Bankiewicz, Philip N Sabes
BACKGROUND: In non-human primate (NHP) optogenetics, infecting large cortical areas with viral vectors is often a difficult and time-consuming task. Previous work has shown that parenchymal delivery of adeno-associated virus (AAV) in the thalamus by convection-enhanced delivery (CED) can lead to large-scale transduction via axonal transport in distal areas including cortex. We used this approach to obtain widespread cortical expression of light-sensitive ion channels. NEW METHOD: AAV vectors co-expressing channelrhodopsin-2 (ChR2) and yellow fluorescent protein (YFP) genes were infused into thalamus of three rhesus macaques under MR-guided CED...
October 16, 2017: Journal of Neuroscience Methods
https://www.readbyqxmd.com/read/28978723/a-murine-model-for-quantitative-real-time-evaluation-of-convection-enhanced-delivery-rt-ced-using-an-18-f-positron-emitting-fluorescent-derivative-of-dasatinib
#9
Melinda Wang, Harikrishna Kommidi, Umberto Tosi, Hua Guo, Zhiping Zhou, Melanie E Schweitzer, Linda Y Wu, Ranjodh Singh, Shengqi Hou, Benedict Law, Richard Ting, Mark M Souweidane
The blood brain barrier can limit the efficacy of systemically delivered drugs in treating neurological malignancies; therefore, alternate routes of drug administration must be considered. The Abl-kinase inhibitor, dasatinib, is modified to give compound 1 ([18F]-1) so that 18F-positron emission tomography (PET) and fluorescent imaging can both be used to observe drug delivery to murine orthotopic glioma. In vitro western blotting, binding studies (IC50 = 22 ± 5 nM), and cell viability assays (IC50 = 46 ± 30 nM) confirm nanomolar, in vitro effectiveness of [18F]-1, a dasatinib derivative that is visible by 18F-PET and fluorescence...
October 4, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28929335/convection-enhanced-delivery-of-sulfasalazine-prolongs-survival-in-a-glioma-stem-cell-brain-tumor-model
#10
Shinya Haryu, Ryuta Saito, Wenting Jia, Takuhiro Shoji, Yui Mano, Aya Sato, Masayuki Kanamori, Yukihiko Sonoda, Oltea Sampetrean, Hideyuki Saya, Teiji Tominaga
Expression of CD44 in glioma cells was previously correlated with tumor grade and is considered a stem cell marker. CD44 stabilizes the cystine-glutamate transporter (xCT) and inhibits apoptosis in cancer stem cells (CSCs). Recently it was found that Sulfasalazine (SSZ), an anti-inflammatory drug, acts as an inhibitor of xCT and therefore has potential as a targeted therapy for CSCs. In this study, we tested an efficacy of SSZ against glioma stem cell model developed in rats. As poor penetration of blood-brain barrier resulted in insufficient efficacy of systemic SSZ treatment, SSZ was delivered locally with convection-enhanced delivery (CED)...
September 19, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28927549/improved-threshold-selection-for-the-determination-of-volume-of-distribution-of-nanoparticles-administered-by-convection-enhanced-delivery
#11
David Lei Chi, Eric Song, Alice Gaudin, W Mark Saltzman
Nanotechnology, in conjunction with convection-enhanced delivery (CED), has gained traction as a promising method to treat many debilitating neurological diseases, including gliomas. One of the key parameters to evaluate the effectiveness of delivery is the volume of distribution (Vd) of nanoparticles within the brain parenchyma. Measurements of Vd are commonly made using fluorescent reporter systems. However, reported analyses lack accurate and robust methods for determining Vd. Current methods face the problems of varying background intensities between images, high intensity aggregates that can shift intensity distributions, and faint residual backgrounds that can occur as artifacts of fluorescent imaging...
August 24, 2017: Computerized Medical Imaging and Graphics: the Official Journal of the Computerized Medical Imaging Society
https://www.readbyqxmd.com/read/28917289/imaging-of-convective-drug-delivery-in-the-nervous-system
#12
REVIEW
Russell R Lonser
Convection-enhanced delivery permits the direct homogeneous delivery of small- and large-molecular-weight putative therapeutics to the nervous system in a manner that bypasses the blood-nervous system barrier. The development of co-infused surrogate imaging tracers (for computed tomography and MRI) allows for the real-time, noninvasive monitoring of infusate distribution during convective delivery. Real-time image monitoring of convective distribution of therapeutic agents insures that targeted structures/nervous system regions are adequately perfused, enhances safety, informs efficacy (or lack thereof) of putative agents, and provides critical information regarding the properties of convection-enhanced delivery in normal and various pathologic tissue states...
October 2017: Neurosurgery Clinics of North America
https://www.readbyqxmd.com/read/28911239/controlled-release-of-liposome-encapsulated-temozolomide-for-brain-tumor-treatment-by-convection-enhanced-delivery
#13
Chung-Yin Lin, Rui-Jin Li, Chiung-Yin Huang, Kuo-Chen Wei, Pin-Yuan Chen
Convection-enhanced delivery (CED) is a promising technique for the delivery of drugs directly into the central nervous system (CNS) and, more specifically, the brain. CED can increase drug concentration within a brain tumor, thereby improving the therapeutic efficacy and limiting the systemic toxicity of tumoricidal agents. In this study, we evaluated a drug-liposome construct in vitro and in vivo using U87 tumor-bearing nude mice. Dipalmitoylphosphatidylcholine (DPPC)-based liposomes were designed to deliver a lipophilic temozolomide (TMZ) formulation (LipoTMZ)...
September 15, 2017: Journal of Drug Targeting
https://www.readbyqxmd.com/read/28885119/volume-of-distribution-and-clearance-of-peptide-based-nanofiber-after-convection-enhanced-delivery
#14
Ranjodh Singh, Vanessa Bellat, Melinda Wang, Melanie E Schweitzer, Y Linda Wu, Ching-Hsuan Tung, Mark M Souweidane, Benedict Law
OBJECTIVE Drug clearance may be a limiting factor in the clinical application of convection-enhanced delivery (CED). Peptide-based nanofibers (NFPs) have a high aspect ratio, and NFPs loaded with drugs could potentially maintain effective drug concentrations for an extended period sufficient for cancer therapy. The objective of this study was to assess the volume of distribution (Vd) and clearance of variable lengths of NFPs when administered using CED. METHODS NFPs composed of multiple methoxypolyethylene glycol (mPEG)-conjugated constructs (mPEG2000-KLDLKLDLKLDL-K( FITC)-CONH2, for which FITC is fluorescein isothiocyanate) were assembled in an aqueous buffer...
September 8, 2017: Journal of Neurosurgery
https://www.readbyqxmd.com/read/28807859/widespread-functional-opsin-transduction-in-the-rat-cortex-via-convection-enhanced-delivery-optimized-for-horizontal-spread
#15
Zeyang Yu, Arto Nurmikko, Ilker Ozden
BACKGROUND: Widespread opsin expression in the cortex of rats, where transgenic models have not been established, is not practical to achieve with the traditional diffusion-based virus transduction methods (DBD). NEW METHOD: We developed protocols for convection-enhanced delivery (CED) of virus for optogenetic transduction of the rat cortex. Targeting the motor forelimb area as an example, we performed dual-site CED (6μL of virus per site, 3mm pitch between sites) in the rat motor cortex...
November 1, 2017: Journal of Neuroscience Methods
https://www.readbyqxmd.com/read/28791656/egfr-as-a-target-for-glioblastoma-treatment-an-unfulfilled-promise
#16
Manfred Westphal, Cecile L Maire, Katrin Lamszus
The receptor for epidermal growth factor (EGFR) is a prime target for cancer therapy across a broad variety of tumor types. As it is a tyrosine kinase, small molecule tyrosine kinase inhibitors (TKIs) targeting signal transduction, as well as monoclonal antibodies against the EGFR, have been investigated as anti-tumor agents. However, despite the long-known enigmatic EGFR gene amplification and protein overexpression in glioblastoma, the most aggressive intrinsic human brain tumor, the potential of EGFR as a target for this tumor type has been unfulfilled...
September 2017: CNS Drugs
https://www.readbyqxmd.com/read/28739449/strategies-to-enhance-the-distribution-of-nanotherapeutics-in-the-brain
#17
Clark Zhang, Panagiotis Mastorakos, Miguel Sobral, Sneha Berry, Eric Song, Elizabeth Nance, Charles G Eberhart, Justin Hanes, Jung Soo Suk
Convection enhanced delivery (CED) provides a powerful means to bypass the blood-brain barrier and drive widespread distribution of therapeutics in brain parenchyma away from the point of local administration. However, recent studies have detailed that the overall distribution of therapeutic nanoparticles (NP) following CED remains poor due to tissue inhomogeneity and anatomical barriers present in the brain, which has limited its translational applicability. Using probe NP, we first demonstrate that a significantly improved brain distribution is achieved by infusing small, non-adhesive NP via CED in a hyperosmolar infusate solution...
July 21, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28696296/multiplexed-rnai-therapy-against-brain-tumor-initiating-cells-via-lipopolymeric-nanoparticle-infusion-delays-glioblastoma-progression
#18
Dou Yu, Omar F Khan, Mario L Suvà, Biqin Dong, Wojciech K Panek, Ting Xiao, Meijing Wu, Yu Han, Atique U Ahmed, Irina V Balyasnikova, Hao F Zhang, Cheng Sun, Robert Langer, Daniel G Anderson, Maciej S Lesniak
Brain tumor-initiating cells (BTICs) have been identified as key contributors to therapy resistance, recurrence, and progression of diffuse gliomas, particularly glioblastoma (GBM). BTICs are elusive therapeutic targets that reside across the blood-brain barrier, underscoring the urgent need to develop novel therapeutic strategies. Additionally, intratumoral heterogeneity and adaptations to therapeutic pressure by BTICs impede the discovery of effective anti-BTIC therapies and limit the efficacy of individual gene targeting...
July 25, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28694032/biodegradable-brain-penetrating-dna-nanocomplexes-and-their-use-to-treat-malignant-brain-tumors
#19
Panagiotis Mastorakos, Clark Zhang, Eric Song, Young Eun Kim, Hee Won Park, Sneha Berry, Won Kyu Choi, Justin Hanes, Jung Soo Suk
The discovery of powerful genetic targets has spurred clinical development of gene therapy approaches to treat patients with malignant brain tumors. However, lack of success in the clinic has been attributed to the inability of conventional gene vectors to achieve gene transfer throughout highly disseminated primary brain tumors. Here, we demonstrate ex vivo that small nanocomplexes composed of DNA condensed by a blend of biodegradable polymer, poly(β-amino ester) (PBAE), with PBAE conjugated with 5kDa polyethylene glycol (PEG) molecules (PBAE-PEG) rapidly penetrate healthy brain parenchyma and orthotopic brain tumor tissues in rats...
July 8, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28686124/influence-of-an-intratumoral-cyst-on-drug-distribution-by-convection-enhanced-delivery-case-report
#20
Iryna Ivasyk, Peter F Morgenstern, Eva Wembacher-Schroeder, Mark M Souweidane
Convection-enhanced delivery (CED) uses positive pressure to induce convective flow of molecules and maximize drug distribution. Concerns have been raised about the effect of cystic structures on uniform drug distribution with CED. The authors describe the case of a patient with a diffuse intrinsic pontine glioma (DIPG) with a large cyst and examine its effect on drug distribution after CED with a radiolabeled antibody. The patient was treated according to protocol with CED of (124)I-8H9 to the pons for nonprogressive DIPG after radiation therapy as part of a Phase I trial (clinical trial registration no...
September 2017: Journal of Neurosurgery. Pediatrics
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