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https://www.readbyqxmd.com/read/28938600/application-of-dual-targeting-drug-delivery-system-for-the-improvement-of-anti-glioma-efficacy-of-doxorubicin
#1
Zhenliang Sun, Xuebing Yan, YiBo Liu, Linsheng Huang, Cheng Kong, Xiao Qu, Man Wang, Renyuan Gao, Huanlong Qin
Chemotherapy of glioma is always hampered by the unsatisfactory tumor accumulation of drugs, of which the most noticeable obstacle is the limited drug permeability from vessels into tumor inner. In the present study, we developed a novel nanocarrier for the delivery of doxorubicin to brain tumor. Such novel drug delivery system was mainly composed of a tumor homing peptide and DOX-loaded PLA nanoparticles (AP1-NP-DOX). CRKRLDRNC peptide, named as AP1, was a newly glioma affinity peptide which could specifically binds to interleukin-4 receptor (IL-4R), highly expressing on both glioma cells and angiogenesis...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938007/neuropilin-1-modulates-tgf%C3%AE-signaling-to-drive-glioblastoma-growth-and-recurrence-after-anti-angiogenic-therapy
#2
Sam C Kwiatkowski, Paola A Guerrero, Shinya Hirota, Zhihua Chen, John E Morales, Manish Aghi, Joseph H McCarty
Glioblastoma (GBM) is a rapidly progressive brain cancer that exploits the neural microenvironment, and particularly blood vessels, for selective growth and survival. Anti-angiogenic agents such as the vascular endothelial growth factor-A (VEGF-A) blocking antibody bevacizumab yield short-term benefits to patients due to blood vessel regression and stabilization of vascular permeability. However, tumor recurrence is common, and this is associated with acquired resistance to bevacizumab. The mechanisms that drive acquired resistance and tumor recurrence in response to anti-angiogenic therapy remain largely unknown...
2017: PloS One
https://www.readbyqxmd.com/read/28935700/mitochondrial-based-therapeutics-for-the-treatment-of-spinal-cord-injury-mitochondrial-biogenesis-as-a-potential-pharmacological-target
#3
Natalie E Scholpa, Rick G Schnellmann
Spinal cord injury (SCI) is characterized by an initial trauma followed by a progressive cascade of damage referred to as secondary injury. A hallmark of secondary injury is vascular disruption leading to vasoconstriction and decreased oxygen delivery, directly reducing the ability of mitochondria to maintain homeostasis, leading to loss of ATP-dependent cellular functions, calcium overload, excitotoxicity and oxidative stress, further exacerbating injury. Restoration of mitochondria dysfunction during the acute phases of secondary injury post-SCI represents a potentially effective therapeutic strategy...
September 21, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28932632/local-endothelial-complement-activation-reverses-endothelial-quiescence-enabling-t-cell-homing-and-tumor-control-during-t-cell-immunotherapy
#4
Andrea Facciabene, Francesco De Sanctis, Stefano Pierini, Edimara S Reis, Klara Balint, John Facciponte, Jens Rueter, Masahiro Kagabu, Paola Magotti, Evripidis Lanitis, Robert A DeAngelis, Ronald J Buckanovich, Wenchao C Song, John D Lambris, George Coukos
Cancer immunotherapy relies upon the ability of T cells to infiltrate tumors. The endothelium constitutes a barrier between the tumor and effector T cells, and the ability to manipulate local vascular permeability could be translated into effective immunotherapy. Here, we show that in the context of adoptive T cell therapy, antitumor T cells, delivered at high enough doses, can overcome the endothelial barrier and infiltrate tumors, a process that requires local production of C3, complement activation on tumor endothelium and release of C5a...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28931753/ask1-dependent-endothelial-cell-activation-is-critical-in-ovarian-cancer-growth-and-metastasis
#5
Mingzhu Yin, Huanjiao Jenny Zhou, Jiqin Zhang, Caixia Lin, Hongmei Li, Xia Li, Yonghao Li, Haifeng Zhang, David G Breckenridge, Weidong Ji, Wang Min
We have recently reported that tumor-associated macrophages (TAMs) promote early transcoelomic metastasis of ovarian cancer by facilitating TAM-ovarian cancer cell spheroid formation. ASK1 is known to be important for macrophage activation and inflammation-mediated tumorigenesis. In the present study, we show that ASK1 deficiency attenuates TAM-spheroid formation and ovarian cancer progression in an orthotopic ovarian cancer model. Interestingly, ASK1 in stroma, but not in TAMs, is critical for peritoneal tumor growth of ovarian cancer...
September 21, 2017: JCI Insight
https://www.readbyqxmd.com/read/28930945/effects-of-propranolol-and-clonidine-on-brain-edema-blood-brain-barrier-permeability-and-endothelial-glycocalyx-disruption-following-fluid-percussion-brain-injury-in-the-rat
#6
Gustav Folmer Genét, Peter Bentzer, Morten Bagge Hansen, Sisse Rye Ostrowski, Pär Ingemar Johansson
BACKGROUND: Traumatic brain injury causes a disruption of the vascular endothelial glycocalyx layer that is associated with an overactivation of the sympathoadrenal system. We hypothesized that early and unselective beta-blockade with propranolol alone or in combination with the alfa2-agonist clonidine would decrease brain edema, blood-brain-barrier permeability and glycocalyx disruption at 24 hours after trauma. METHODS: We subjected fifty-three adult male Sprague-Dawley rats to lateral fluid-percussion brain injury and randomized infusion with propranolol (n=16), propranolol+clonidine (n=16), vehicle (n=16) or sham (n=5) for 24 hours...
September 20, 2017: Journal of Trauma and Acute Care Surgery
https://www.readbyqxmd.com/read/28930571/role-of-pericytes-in-vascular-immunosurveillance
#7
Konstantin Stark, Kami Pekayvaz, Steffen Massberg
Pericytes build together with endothelial cells the microvascular vessel wall. They have been mainly implicated in angiogenesis and maintenance of the blood brain barrier, but there is accumulating evidence for an immunological function of pericytes. Occupying a strategic position between the blood stream and the interstitial space, pericytes are able to sense environmental cues from both sides in an organ-specific manner and serve as gatekeepers for innate immune cells. In addition, pericytes are able to interact with leukocytes mediated by adhesion molecules as well as chemokines and are involved from the development of leukocytes in the bone marrow to their migration to injured or infected areas in target tissues...
January 1, 2018: Frontiers in Bioscience (Landmark Edition)
https://www.readbyqxmd.com/read/28929580/selective-expression-of-egfp-in-mouse-perivascular-astrocytes-by-modification-of-the-mlc1-gene-using-t2a-based-ribosome-skipping
#8
Jordan J Toutounchian, Joseph H McCarty
Perivascular astrocyte end feet closely juxtapose cerebral blood vessels to regulate important developmental and physiological processes including endothelial cell proliferation and sprouting as well as the formation of the blood-brain barrier (BBB). The mechanisms underlying these events remain largely unknown due to a lack of experimental models for identifying perivascular astrocytes and distinguishing these cell types from other astroglial populations. Megalencephalic leukoencephalopathy with subcortical cysts 1 (Mlc1) is a transmembrane protein that is expressed in perivascular astrocyte end feet where it controls BBB development and homeostasis...
September 20, 2017: Genesis: the Journal of Genetics and Development
https://www.readbyqxmd.com/read/28923916/critical-role-of-caveolin-1-in-ocular-neovascularization-and-multitargeted-antiangiogenic-effects-of-cavtratin-via-jnk
#9
Yida Jiang, Xianchai Lin, Zhongshu Tang, Chunsik Lee, Geng Tian, Yuxiang Du, Xiangke Yin, Xiangrong Ren, Lijuan Huang, Zhimin Ye, Wei Chen, Fan Zhang, Jia Mi, Zhiqin Gao, Shasha Wang, Qishan Chen, Liying Xing, Bin Wang, Yihai Cao, William C Sessa, Rong Ju, Yizhi Liu, Xuri Li
Ocular neovascularization is a devastating pathology of numerous ocular diseases and is a major cause of blindness. Caveolin-1 (Cav-1) plays important roles in the vascular system. However, little is known regarding its function and mechanisms in ocular neovascularization. Here, using comprehensive model systems and a cell permeable peptide of Cav-1, cavtratin, we show that Cav-1 is a critical player in ocular neovascularization. The genetic deletion of Cav-1 exacerbated and cavtratin administration inhibited choroidal and retinal neovascularization...
September 18, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28919014/regulation-and-function-of-endothelial-glycocalyx-layer-in-vascular-diseases
#10
REVIEW
Irina Sieve, Anja Münster-Kühnel, Denise Hilfiker-Kleiner
In the vascular system, the endothelial surface layer (ESL) as the inner surface of blood vessels affects mechanotransduction, vascular permeability, rheology, thrombogenesis, and leukocyte adhesion. It creates barriers between endothelial cells and blood and neighbouring cells. The glycocalyx, composed of glycoconjugates and proteoglycans, is an integral component of the ESL and a key element in inter- and intracellular communication and tissue homeostasis. In pathophysiological conditions (atherosclerosis, infection, ischemia/reperfusion injury, diabetes, trauma and acute lung injury) glycocalyx-degrading factors, i...
September 12, 2017: Vascular Pharmacology
https://www.readbyqxmd.com/read/28912284/t1-weighted-dynamic-contrast-enhanced-mr-perfusion-imaging-characterizes-tumor-response-to-radiation-therapy-in-chordoma
#11
P Santos, K K Peck, J Arevalo-Perez, S Karimi, E Lis, Y Yamada, A I Holodny, J Lyo
BACKGROUND AND PURPOSE: Chordomas notoriously demonstrate a paucity of changes following radiation therapy on conventional MR imaging. We hypothesized that dynamic contrast-enhanced MR perfusion imaging parameters of chordomas would change significantly following radiation therapy. MATERIALS AND METHODS: Eleven patients with pathology-proved chordoma who completed dynamic contrast-enhanced MR perfusion imaging pre- and postradiation therapy were enrolled. Quantitative tumor measurements were obtained by 2 attending neuroradiologists...
September 14, 2017: AJNR. American Journal of Neuroradiology
https://www.readbyqxmd.com/read/28912161/disruption-of-bmal1-impairs-blood-brain-barrier-integrity-via-pericyte-dysfunction
#12
Ryota Nakazato, Kenji Kawabe, Daisuke Yamada, Shinsuke Ikeno, Michihiro Mieda, Shigeki Shimba, Eiichi Hinoi, Yukio Yoneda, Takeshi Takarada
Circadian rhythm disturbances are well-established in neurological diseases. However, how these disruptions cause homeostatic imbalances remains poorly understood. Brain and muscle aryl hydrocarbon receptor nuclear translocator-like protein 1 (Bmal1) is a major circadian clock transcriptional activator, and Bmal1 deficiency in male Bmal1nestin(-/-) mice induced marked astroglial activation without affecting the number of astrocytes in the brain and spinal cord. Bmal1 deletion caused blood-brain barrier (BBB) hyperpermeability with an age-dependent loss of pericyte coverage of blood vessels in the brain...
September 14, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28904739/role-of-oxidative-stress-and-mitochondrial-dysfunction-in-sepsis-and-potential-therapies
#13
REVIEW
Konstantinos Mantzarlis, Vasiliki Tsolaki, Epaminondas Zakynthinos
Sepsis is one of the most important causes of death in intensive care units. Despite the fact that sepsis pathogenesis remains obscure, there is increasing evidence that oxidants and antioxidants play a key role. The imbalance of the abovementioned substances in favor of oxidants is called oxidative stress, and it contributes to sepsis process. The most important consequences are vascular permeability impairment, decreased cardiac performance, and mitochondrial malfunction leading to impaired respiration. Nitric oxide is perhaps the most important and well-studied oxidant...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28904478/how-useful-is-extravascular-lung-water-measurement-in-managing-lung-injury-in-intensive-care-unit
#14
Anirban Bhattacharjee, Debasis Pradhan, Prithwis Bhattacharyya, Samarjit Dey, Daniala Chhunthang, Akash Handique, Angkita Barman, Mohd Yunus
CONTEXT: The primary goal of septic shock management is optimization of organ perfusion, often at the risk of overloading the interstitium and causing pulmonary edema. The conventionally used end points of resuscitation do not generally include volumetric parameters such as extravascular lung water index (EVLWI) and pulmonary vascular permeability index (PVPI). AIMS: This study aimed to assess the prognostic value of EVLWI and PVPI by calculating their correlation with the severity of lung injury...
August 2017: Indian Journal of Critical Care Medicine
https://www.readbyqxmd.com/read/28901449/fk506-suppresses-hypoxia%C3%A2-induced-inflammation-and-protects-tight-junction-function-via-the-can%C3%A2-nfatc1-signaling-pathway-in-retinal-microvascular-epithelial-cells
#15
Yaguang Hu, Boyu Yang, Yue Xu, Li Jiang, Ching-Kit Tsui, Xiaoling Liang
The present study aimed to identify whether FK506 suppresses hypoxia‑induced inflammation and protects tight junction function via the calcineurin‑nuclear factor of activated T‑cells 1 (CaN‑NFATc1) signaling pathway in mouse retinal microvascular endothelial cells (mRMECs). The mRMECs were treated with FK506 at different concentrations following the induction of hypoxia. Trans‑epithelial electrical resistance (TEER) and cell permeability were examined to measure the integrity of the tight junctions...
September 12, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28900088/-estimation-of-time-dependent-microrna-expression-patterns-in-brain-tissue-leukocytes-and-blood-plasma-of-rats-under-photochemically-induced-focal-cerebral-ischemia
#16
V A Gusar, A V Timofeeva, I S Zhanin, S I Shram, V G Pinelis
miRNA expression over different time periods (24 and 48 h) using the quantitative RT-PCR and deep sequencing has been evaluated in a model of photochemically induced thrombosis. A combination of two approaches allowed us to determine the miRNA expression patterns caused by ischemia. Nine miRNAs, including let-7f-5p, miR-221-3p, miR-21-5p, miR-30c-5p, miR-30a-3p, miR-223-3p, miR-23a-3p, miR-22-5p, and miR-99a-5p, were differentially expressed in brain tissue and leukocytes of rats 48 h after onset of ischemia...
July 2017: Molekuliarnaia Biologiia
https://www.readbyqxmd.com/read/28899758/chronic-global-analysis-of-vascular-permeability-and-cerebral-blood-flow-after-bone-marrow-stromal-cell-treatment-of-traumatic-brain-injury-in-the-rat-a-long-term-mri-study
#17
Lian Li, Michael Chopp, Guangliang Ding, Qingjiang Li, Asim Mahmood, Quan Jiang
Vascular permeability and hemodynamic alteration in response to the transplantation of human bone marrow stromal cells (hMSCs) after traumatic brain injury (TBI) were longitudinally investigated in non directly injured and normal-appearing cerebral tissue using magnetic resonance imaging (MRI). Male Wistar rats (300-350g, n=30) subjected to controlled cortical impact TBI were intravenously injected with 1 ml of saline (at 6-hours or 1-week post-injury, n=5/group) or with hMSCs in suspension (∼3x10(6) hMSCs, at 6-hours or 1-week post-injury, n=10/group)...
September 9, 2017: Brain Research
https://www.readbyqxmd.com/read/28890699/sphingosine-1-phosphate-signaling-as-a-target-in-hepatic-fibrosis-therapy
#18
REVIEW
Bárbara González-Fernández, Diana I Sánchez, Javier González-Gallego, María J Tuñón
Liver fibrosis is an excess production of extracellular matrix proteins as a result of chronic liver disease which leads to cell death and organ dysfunction. The key cells involved in fibrogenesis are resident hepatic stellate cells (HSCs) which are termed myofibroblasts after activation, acquiring contractile, proliferative, migratory and secretory capability. Sphingosine 1-phosphate (S1P) is a bioactive sphingolipid with well-established effects on angiogenesis, carcinogenesis and immunity. Accumulating evidence demonstrates that this metabolite is involved in the profibrotic inflammatory process through the regulation of pleiotropic cell responses, such as vascular permeability, leukocyte infiltration, cell survival, migration, proliferation and HSCs differentiation to myofibroblasts...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28887355/altered-vasculature-in-bone-marrow-drives-leukemogenesis
#19
(no author information available yet)
Nitric oxide promotes vascular permeability and hypoxia in the bone marrow to drive AML.
September 8, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28887206/reproducibility-and-relative-stability-in-magnetic-resonance-imaging-indices-of-tumor-vascular-physiology-over-a-period-of-24h-in-a-rat-9l-gliosarcoma-model
#20
Tavarekere N Nagaraja, Rasha Elmghirbi, Stephen L Brown, Lonni R Schultz, Ian Y Lee, Kelly A Keenan, Swayamprava Panda, Glauber Cabral, Tom Mikkelsen, James R Ewing
PURPOSE: The objective was to study temporal changes in tumor vascular physiological indices in a period of 24h in a 9L gliosarcoma rat model. METHODS: Fischer-344 rats (N=14) were orthotopically implanted with 9L cells. At 2weeks post-implantation, they were imaged twice in a 24h interval using dynamic contrast enhanced magnetic resonance imaging (DCE-MRI). Data-driven model-selection-based analysis was used to segment tumor regions with varying vascular permeability characteristics...
September 5, 2017: Magnetic Resonance Imaging
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