scholarly journals Development of curcumin-loaded zein nanoparticles for transport across the blood–brain barrier and inhibition of glioblastoma cell growth

2021 ◽  
Author(s):  
Huaiying Zhang ◽  
Winant L. van Os ◽  
Xiaobo Tian ◽  
Guangyue Zu ◽  
Laís Ribovski ◽  
...  
Keyword(s):  
Cell Growth ◽  
Blood Brain Barrier ◽  
Glioma Cells ◽  
C6 Glioma ◽  
Brain Barrier ◽  
C6 Glioma Cells ◽  
Glioblastoma Cell ◽  
Tumor Spheroids ◽  
Blood Brain

Zein-polydopamine nanoparticles functionalized with G23 peptide cross an in vitro blood–brain barrier and penetrate tumor spheroids. When loaded with curcumin they effectively reduce proliferation, migration, and viability of C6 glioma cells.

scholarly journals Mechanisms of edema formation after intracerebral hemorrhage: effects of thrombin on cerebral blood flow, blood-brain barrier permeability, and cell survival in a rat model

1996 ◽  
Vol 1 (4) ◽  
pp. E3 ◽  
Author(s):  
Kevin R. Lee ◽  
Nobuyuki Kawai ◽  
Seoung Kim ◽  
Oren Sagher ◽  
Julian T. Hoff
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Intracerebral Hemorrhage ◽  
Blood Brain Barrier ◽  
Brain Slices ◽  
Brain Barrier ◽  
C6 Glioma Cells ◽  
Edema Formation ◽  
Blood Brain

Recently, the authors showed that thrombin contributes to the formation of brain edema following intracerebral hemorrhage. The current study examines whether the action of thrombin is due to an effect on cerebral blood flow (CBF), vasoreactivity, blood-brain barrier (BBB) function, or cell viability. In vivo solutions of thrombin were infused stereotactically into the right basal ganglia of rats. The animals were sacrificed 24 hours later; CBF and BBB permeability were measured. The actions of thrombin on vasoreactivity were examined in vitro by superfusing thrombin on cortical brain slices while monitoring microvessel diameter with videomicroscopy. In separate experiments C6 glioma cells were exposed to various concentrations of thrombin and lactate dehydrogenase release, a marker of cell death, was measured. The results indicate that thrombin induces BBB disruption as well as death of parenchymal cells, whereas CBF and vasoreactivity are not altered. The authors conclude that cell toxicity and BBB disruption by thrombin are triggering mechanisms for the edema formation that follows intracerebral hemorrhage.

scholarly journals Monotherapy efficacy of blood–brain barrier permeable small molecule reactivators of protein phosphatase 2A in glioblastoma

2020 ◽  
Vol 2 (1) ◽  
Author(s):  
Joni Merisaari ◽  
Oxana V Denisova ◽  
Milena Doroszko ◽  
Vadim Le Joncour ◽  
Patrik Johansson ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Cell Lines ◽  
Small Molecule ◽  
Protein Phosphatase ◽  
Protein Phosphatase 2A ◽  
Brain Barrier ◽  
Glioblastoma Cell ◽  
Blood Brain ◽  
Phosphatase 2A

Abstract Glioblastoma is a fatal disease in which most targeted therapies have clinically failed. However, pharmacological reactivation of tumour suppressors has not been thoroughly studied as yet as a glioblastoma therapeutic strategy. Tumour suppressor protein phosphatase 2A is inhibited by non-genetic mechanisms in glioblastoma, and thus, it would be potentially amendable for therapeutic reactivation. Here, we demonstrate that small molecule activators of protein phosphatase 2A, NZ-8-061 and DBK-1154, effectively cross the in vitro model of blood–brain barrier, and in vivo partition to mouse brain tissue after oral dosing. In vitro, small molecule activators of protein phosphatase 2A exhibit robust cell-killing activity against five established glioblastoma cell lines, and nine patient-derived primary glioma cell lines. Collectively, these cell lines have heterogeneous genetic background, kinase inhibitor resistance profile and stemness properties; and they represent different clinical glioblastoma subtypes. Moreover, small molecule activators of protein phosphatase 2A were found to be superior to a range of kinase inhibitors in their capacity to kill patient-derived primary glioma cells. Oral dosing of either of the small molecule activators of protein phosphatase 2A significantly reduced growth of infiltrative intracranial glioblastoma tumours. DBK-1154, with both higher degree of brain/blood distribution, and more potent in vitro activity against all tested glioblastoma cell lines, also significantly increased survival of mice bearing orthotopic glioblastoma xenografts. In summary, this report presents a proof-of-principle data for blood–brain barrier—permeable tumour suppressor reactivation therapy for glioblastoma cells of heterogenous molecular background. These results also provide the first indications that protein phosphatase 2A reactivation might be able to challenge the current paradigm in glioblastoma therapies which has been strongly focused on targeting specific genetically altered cancer drivers with highly specific inhibitors. Based on demonstrated role for protein phosphatase 2A inhibition in glioblastoma cell drug resistance, small molecule activators of protein phosphatase 2A may prove to be beneficial in future glioblastoma combination therapies.

Influence of glioma cells on a new co-culture in vitro blood–brain barrier model for characterization and validation of permeability

2015 ◽  
Vol 490 (1-2) ◽  
pp. 94-101 ◽  
Author(s):  
Bárbara Mendes ◽  
Cláudia Marques ◽  
Isabel Carvalho ◽  
Paulo Costa ◽  
Susana Martins ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Glioma Cells ◽  
Brain Barrier ◽  
Culture In Vitro ◽  
Blood Brain ◽  
Blood Brain Barrier Model ◽  
Barrier Model

Mechanisms of edema formation after intracerebral hemorrhage: effects of thrombin on cerebral blood flow, blood-brain barrier permeability, and cell survival in a rat model

1997 ◽  
Vol 86 (2) ◽  
pp. 272-278 ◽  
Author(s):  
Kevin R. Lee ◽  
Nobuyuki Kawai ◽  
Seoung Kim ◽  
Oren Sagher ◽  
Julian T. Hoff
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Intracerebral Hemorrhage ◽  
Blood Brain Barrier ◽  
Brain Slices ◽  
Brain Barrier ◽  
C6 Glioma Cells ◽  
Edema Formation ◽  
Blood Brain

✓ Recently, the authors showed that thrombin contributes to the formation of brain edema following intracerebral hemorrhage. The current study examines whether the action of thrombin is due to an effect on cerebral blood flow (CBF), vasoreactivity, blood-brain barrier (BBB) function, or cell viability. In vivo solutions of thrombin were infused stereotactically into the right basal ganglia of rats. The animals were sacrificed 24 hours later; CBF and BBB permeability were measured. The actions of thrombin on vasoreactivity were examined in vitro by superfusing thrombin on cortical brain slices while monitoring microvessel diameter with videomicroscopy. In separate experiments C6 glioma cells were exposed to various concentrations of thrombin, and lactate dehydrogenase release, a marker of cell death, was measured. The results indicate that thrombin induces BBB disruption as well as death of parenchymal cells, whereas CBF and vasoreactivity are not altered. The authors conclude that cell toxicity and BBB disruption by thrombin are triggering mechanisms for the edema formation that follows intracerebral hemorrhage.

scholarly journals CYT387, a potent IKBKE inhibitor, suppresses human glioblastoma progression by activating the Hippo pathway

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Xin Wang ◽  
Jie Lu ◽  
Jing Li ◽  
Yang Liu ◽  
Gaochao Guo ◽  
...  
Keyword(s):  
Tumor Progression ◽  
Blood Brain Barrier ◽  
Hippo Pathway ◽  
Brain Barrier ◽  
Migration And Invasion ◽  
Mouse Tumor ◽  
Glioblastoma Cell ◽  
Blood Brain ◽  
The Hippo Pathway

AbstractRecent studies have showed that IKBKE is overexpressed in several kinds of cancers and that IKBKE-knockdown inhibits tumor progression. In this article, we first verified that two glioblastoma cell lines, U87-MG and LN-229, were sensitive to CYT387 by measuring the half maximal inhibitory concentration (IC50) with a CCK-8 assay and then demonstrated that CYT387, as a potent IKBKE inhibitor, suppressed glioblastoma cell proliferation, migration and invasion. Additionally, CYT387 induced cell apoptosis and arrested the cell cycle at the G2/M checkpoint in vitro. Furthermore, we showed that CYT387 did not simply inhibit IKBKE activity but also decreased IKBKE expression at the protein level rather than at the mRNA level. We discovered that CYT387 restrained malignant tumor progression by activating the Hippo pathway in vitro. By coimmunoprecipitation (co-IP), we showed that IKBKE interacted with TEAD2 and YAP1, thus accelerating TEAD2 and YAP1 transport into the nucleus. In subsequent in vivo experiments, we found that CYT387 inhibited subcutaneous nude mouse tumor growth but had little impact on intracranial orthotopic xenografts, probably due to a limited ability to penetrate the blood–brain barrier (BBB). These results suggest that CYT387 has potential as a new antiglioblastoma drug, but an approach to allow passage through the blood–brain barrier (BBB) is needed.

scholarly journals Optimization of endothelial cell growth in a murine in vitro blood-brain barrier model

2011 ◽  
Vol 7 (3) ◽  
pp. 409-417 ◽  
Author(s):  
Diane M. Wuest ◽  
Kelvin H. Lee
Keyword(s):  
Endothelial Cell ◽  
Cell Growth ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Blood Brain ◽  
Blood Brain Barrier Model ◽  
Endothelial Cell Growth ◽  
Barrier Model

scholarly journals Development of Real-Time Transendothelial Electrical Resistance Monitoring for an In Vitro Blood-Brain Barrier System

Micromachines ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 37
Author(s):  
Kai-Hong Tu ◽  
Ling-Shan Yu ◽  
Zong-Han Sie ◽  
Han-Yi Hsu ◽  
Khuloud T. Al-Jamal ◽  
...  
Keyword(s):  
Cell Growth ◽  
Real Time ◽  
Blood Brain Barrier ◽  
Electrical Resistance ◽  
Angle Measurement ◽  
Brain Barrier ◽  
Transendothelial Electrical Resistance ◽  
Blood Brain ◽  
On Chip

Three-dimensional (3D) cell cultures and organs-on-a-chip have been developed to construct microenvironments that resemble the environment within the human body and to provide a platform that enables clear observation and accurate assessments of cell behavior. However, direct observation of transendothelial electrical resistance (TEER) has been challenging. To improve the efficiency in monitoring the cell development in organs-on-a-chip, in this study, we designed and integrated commercially available TEER measurement electrodes into an in vitro blood-brain barrier (BBB)-on-chip system to quantify TEER variation. Moreover, a flowing culture medium was added to the monolayered cells to simulate the promotion of continuous shear stress on cerebrovascular cells. Compared with static 3D cell culture, the proposed BBB-on-chip integrated with electrodes could measure TEER in a real-time manner over a long period. It also allowed cell growth angle measurement, providing instant reports of cell growth information online. Overall, the results demonstrated that the developed system can aid in the quantification of the continuous cell-pattern variations for future studies in drug testing.

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