Blood flow and blood-to-tissue transport in 9L gliosarcomas: the role of the brain tumor model in drug delivery research

1991 ◽  
Vol 11 (3) ◽  
pp. 185-197 ◽  
Author(s):  
Robin D. Fross ◽  
Peter C. Warnke ◽  
Dennis R. Groothuis
Keyword(s):  
Drug Delivery ◽  
Blood Flow ◽  
Brain Tumor ◽  
Tumor Model ◽  
Brain Tumor Model ◽  
The Brain

scholarly journals SCIDOT-33. ULTRASOUND-FACILITATED DRUG DELIVERY DEVICE FOR LOCAL DRUG INFUSION AGAINST BRAIN TUMORS

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi278-vi278
Author(s):  
Ryuta Saito ◽  
Wenting Jia ◽  
Aya Sato ◽  
Kenji Inoue ◽  
Saori Okuno ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Brain Tumor ◽  
Resonance Frequency ◽  
First Generation ◽  
Second Generation ◽  
Drug Distribution ◽  
Tumor Model ◽  
Driving Voltage ◽  
Brain Tumor Model ◽  
The Brain

Abstract OBJECT Local drug delivery into brain tumor faces a major problem: limitations of distribution. Recently, we have been working to develop a novel treatment strategy delivering chemotherapeutic agents directly into the tumor. Previously, we developed an ultrasound facilitated drug delivery (UFD) system in order to achieve extensive drug distribution (J Neurosurg 124, 2016). Subsequently, we fabricated a second-generation device by analyzing optimal ultrasound generating condition. Here, we tested the intraparenchymal and intratumoral drug distribution using the device. METHODS Resonance frequency of the device was determined by measuring the strength of sound field using hydrophone in water. Using the UFD system, applying resonance frequency, evans blue dye was infused into the striatum of Fisher344 rats. Immediately after the infusion, brains were harvested, quickly frozen, and sectioned to evaluate the distributions of the dye. Similar study was then performed in 9L brain tumor model. RESULTS The second-generation device successfully distributed the dye to the volume 1.5~2 times larger than simple CED with using half the driving voltage than first-generation device. Moreover, the distribution instability, which was a major problem with the first-generation device, was resolved achieving smaller standard deviation. Using multiple resonance frequencies of the device, we found the difference in drug distribution; suggesting the existence of optimal frequencies for brain interstitial drug delivery. This drug delivery strategy also worked in brain tumor model increasing the coverage inside the brain tumor. CONCLUSIONS The second generation UFD device successfully and stably achieved enlarged distribution in the brain parenchyma and in the brain tumor.

Effects of Hyperglycemia on pH and Blood Flow In a Brain Tumor Model: An In Vivo Study

1989 ◽  
Vol 24 (12) ◽  
pp. S96
Author(s):  
S L Mitchell ◽  
B D Ross ◽  
H Merkle ◽  
M Garwood
Keyword(s):  
Blood Flow ◽  
Brain Tumor ◽  
Tumor Model ◽  
In Vivo Study ◽  
Brain Tumor Model

Distribution of hematoporphyrin derivative in the rat 9L gliosarcoma brain tumor analyzed by digital video fluorescence microscopy

1984 ◽  
Vol 61 (6) ◽  
pp. 1113-1119 ◽  
Author(s):  
James E. Boggan ◽  
Robert Walter ◽  
Michael S. B. Edwards ◽  
Janis K. Borcich ◽  
Richard L. Davis ◽  
...  
Keyword(s):  
Brain Tumor ◽  
Tumor Model ◽  
Normal Brain ◽  
Hematoporphyrin Derivative ◽  
Content Type ◽  
9L Gliosarcoma ◽  
Video Fluorescence Microscopy ◽  
Brain Tumor Model ◽  
The Brain ◽  
Fine Print

✓ A digital video fluorescence microscopy technique was used to evaluate the distribution of hematoporphyrin derivative (HPD) in the rat intracerebral 9L gliosarcoma brain-tumor model at 4, 24, 48, and 72 hours after intravenous administration of 10 mg/kg of the drug. Compared to surrounding normal brain, there was significant preferential uptake of HPD into the tumor. In sections surveyed, fluorescence reached a maximum value by 24 hours; however, only 33% to 44% of the tumor was fluorescent. In contrast, fluorescence within the surrounding normal brain was maximum at 4 hours, but was present in less than 1% of the brain tissue evaluated. The effect of HPD sensitization to a laser light dose (633 nm) of 30 joules/sq cm delivered through the intact skull was evaluated histologically in 10 rats. A patchy coagulation necrosis, possibly corresponding to the distribution of HPD fluorescence seen within the tumor, was observed. There was evidence that photoradiation therapy (PRT) affects defective tumor vasculature and that a direct tumor cell toxicity spared normal brain tissue. Despite these findings, limited uptake of HPD in tumor and the brain adjacent to tumor may decrease the effectiveness of PRT in the 9L gliosarcoma brain-tumor model. Because of the similarity between the capillary system of the 9L tumor and human brain tumors, PRT may have a limited therapeutic effect in patients with malignant brain tumors.

scholarly journals Ultrasmall Core-Shell Silica Nanoparticles for Precision Drug Delivery in a High-Grade Malignant Brain Tumor Model

2019 ◽  
Vol 26 (1) ◽  
pp. 147-158 ◽  
Author(s):  
Rupa Juthani ◽  
Brian Madajewski ◽  
Barney Yoo ◽  
Li Zhang ◽  
Pei-Ming Chen ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Brain Tumor ◽  
Silica Nanoparticles ◽  
Tumor Model ◽  
Malignant Brain Tumor ◽  
Core Shell ◽  
High Grade ◽  
Brain Tumor Model

Novel Phospholipid-Based Labrasol Nanomicelles Loaded Flavonoids for Oral Delivery with Enhanced Penetration and Anti-Brain Tumor Efficiency

2020 ◽  
Vol 17 (3) ◽  
pp. 229-245
Author(s):  
Gang Wang ◽  
Junjie Wang ◽  
Rui Guan
Keyword(s):  
Drug Delivery ◽  
Brain Tumor ◽  
Oral Delivery ◽  
Safe Delivery ◽  
Drug Delivery Vehicles ◽  
Therapeutic Benefits ◽  
Delivery Vehicles ◽  
The Brain

Background: Owing to the rich anticancer properties of flavonoids, there is a need for their incorporation into drug delivery vehicles like nanomicelles for safe delivery of the drug into the brain tumor microenvironment. Objective: This study, therefore, aimed to prepare the phospholipid-based Labrasol/Pluronic F68 modified nano micelles loaded with flavonoids (Nano-flavonoids) for the delivery of the drug to the target brain tumor. Methods: Myricetin, quercetin and fisetin were selected as the initial drugs to evaluate the biodistribution and acute toxicity of the drug delivery vehicles in rats with implanted C6 glioma tumors after oral administration, while the uptake, retention, release in human intestinal Caco-2 cells and the effect on the brain endothelial barrier were investigated in Human Brain Microvascular Endothelial Cells (HBMECs). Results: The results demonstrated that nano-flavonoids loaded with myricetin showed more evenly distributed targeting tissues and enhanced anti-tumor efficiency in vivo without significant cytotoxicity to Caco-2 cells and alteration in the Trans Epithelial Electric Resistance (TEER). There was no pathological evidence of renal, hepatic or other organs dysfunction after the administration of nanoflavonoids, which showed no significant influence on cytotoxicity to Caco-2 cells. Conclusion: In conclusion, Labrasol/F68-NMs loaded with MYR and quercetin could enhance antiglioma effect in vitro and in vivo, which may be better tools for medical therapy, while the pharmacokinetics and pharmacodynamics of nano-flavonoids may ensure optimal therapeutic benefits.

Quantitative Measurements of Regional Glucose Utilization and Rate of Valine Incorporation into Proteins by Double-Tracer Autoradiography in the Rat Brain Tumor Model

1989 ◽  
Vol 9 (1) ◽  
pp. 87-95 ◽  
Author(s):  
Michihiro Kirikae ◽  
Mirko Diksic ◽  
Y. Lucas Yamamoto
Keyword(s):  
Protein Synthesis ◽  
Brain Tumor ◽  
Rat Brain ◽  
Brain Tissue ◽  
Glucose Utilization ◽  
Tumor Model ◽  
Normal Brain ◽  
Normal Brain Tissue ◽  
Rat Brain Tumor ◽  
Brain Tumor Model

We examined the rate of glucose utilization and the rate of valine incorporation into proteins using 2-[18F]fluoro-2-deoxyglucose and L-[1-14C]-valine in a rat brain tumor model by quantitative double-tracer autoradiography. We found that in the implanted tumor the rate of valine incorporation into proteins was about 22 times and the rate of glucose utilization was about 1.5 times that in the contralateral cortex. (In the ipsilateral cortex, the tumor had a profound effect on glucose utilization but no effect on the rate of valine incorporation into proteins.) Our findings suggest that it is more useful to measure protein synthesis than glucose utilization to assess the effectiveness of antitumor agents and their toxicity to normal brain tissue. We compared two methods to estimate the rate of valine incorporation: “kinetic” (quantitation done using an operational equation and the average brain rate coefficients) and “washed slices” (unbound labeled valine removed by washing brain slices in 10% thrichloroacetic acid). The results were the same using either method. It would seem that the kinetic method can thus be used for quantitative measurement of protein synthesis in brain tumors and normal brain tissue using [11C]-valine with positron emission tomography.

scholarly journals Vascular phenotyping of brain tumors using magnetic resonance microscopy (μMRI)

2011 ◽  
Vol 31 (7) ◽  
pp. 1623-1636 ◽  
Author(s):  
Eugene Kim ◽  
Jiangyang Zhang ◽  
Karen Hong ◽  
Nicole E Benoit ◽  
Arvind P Pathak
Keyword(s):  
Brain Tumor ◽  
Magnetic Resonance ◽  
Brain Tumors ◽  
Three Dimensional ◽  
Region Of Interest ◽  
Tumor Model ◽  
Magnetic Resonance Microscopy ◽  
Vascular Phenotype ◽  
Brain Tumor Model ◽  
Novel Method

Abnormal vascular phenotypes have been implicated in neuropathologies ranging from Alzheimer's disease to brain tumors. The development of transgenic mouse models of such diseases has created a crucial need for characterizing the murine neurovasculature. Although histologic techniques are excellent for imaging the microvasculature at submicron resolutions, they offer only limited coverage. It is also challenging to reconstruct the three-dimensional (3D) vasculature and other structures, such as white matter tracts, after tissue sectioning. Here, we describe a novel method for 3D whole-brain mapping of the murine vasculature using magnetic resonance microscopy (μMRI), and its application to a preclinical brain tumor model. The 3D vascular architecture was characterized by six morphologic parameters: vessel length, vessel radius, microvessel density, length per unit volume, fractional blood volume, and tortuosity. Region-of-interest analysis showed significant differences in the vascular phenotype between the tumor and the contralateral brain, as well as between postinoculation day 12 and day 17 tumors. These results unequivocally show the feasibility of using μMRI to characterize the vascular phenotype of brain tumors. Finally, we show that combining these vascular data with coregistered images acquired with diffusion-weighted MRI provides a new tool for investigating the relationship between angiogenesis and concomitant changes in the brain tumor microenvironment.

scholarly journals MRI assessment of hemodynamic effects of angiopoietin-2 overexpression in a brain tumor model

2009 ◽  
Vol 11 (5) ◽  
pp. 488-502 ◽  
Author(s):  
Samuel Valable ◽  
Dauphou Eddi ◽  
Jean-Marc Constans ◽  
Jean-Sébastien Guillamo ◽  
Myriam Bernaudin ◽  
...  
Keyword(s):  
Brain Tumor ◽  
Tumor Model ◽  
Hemodynamic Effects ◽  
Brain Tumor Model ◽  
Angiopoietin 2
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