scholarly journals Cranial Transposition and Revascularization of Autologous Omentum: A Novel Surgical Technique for Bypassing the Blood Brain Barrier after Resection of Recurrent Glioblastoma Multiforme

2021 ◽  
Author(s):  
Omer Doron ◽  
Tom Chen ◽  
Tamika Wong ◽  
Amy Tucker ◽  
Peter Constantino ◽  
...  
Keyword(s):  
Glioblastoma Multiforme ◽  
Blood Brain Barrier ◽  
Free Flap ◽  
Tumor Resection ◽  
Chemotherapeutic Agents ◽  
Brain Barrier ◽  
External Carotid ◽  
Cerebral Angiogram ◽  
Resection Cavity ◽  
Blood Brain

Abstract Background: Glioblastoma multiforme (GBM) patients continue to suffer a poor prognosis. The blood brain barrier (BBB) comprises one of the obstacles for therapy, creating a barrier that decreases the bioavailability of chemotherapeutic agents in the central nervous system. Previously, a vascularized temporoparietal fascial scalp flap (TPFF) lining the resection cavity was introduced in a trial conducted in our institution, in newly-diagnosed GBM patients in an attempt to bypass the BBB after initial resection. In this paper, we report on a new technique to bypass the BBB after re-resection and potentially to allow tumor antigens to be surveilled by the immune system .Objective: Assess the feasibility of performing a cranial transposition and revascularization of autologous omentum after re-resection of GBM.Methods: Laparoscopically harvested omental free flap was transposed to the resection cavity by a team consisting of neurosurgeons, otolaryngologists, and general surgeons. This was done as part of a single center, single arm, open-label, phase I study.Results: Autologous abdominal omental tissue was harvested laparoscopically on its vascularized pedicle in 2 patients, transposed as a free flap, revascularized using external carotid artery, and carefully laid into the tumor resection cavity. Patients did well postoperatively returning to baseline activities. Graft viability was confirmed by cerebral angiogram. Conclusion: Omental cranial transposition of a laparoscopically harvested, vascularized flap, into the cavity of re-resected GBM patients is feasible and safe in the short term. Further studies are needed to ascertain whether such technique can improve progression free survival and overall survival in these patients.

scholarly journals Safety and feasibility of multiple blood-brain barrier disruptions for the treatment of glioblastoma in patients undergoing standard adjuvant chemotherapy

2020 ◽  
pp. 1-9 ◽  
Author(s):  
So Hee Park ◽  
Myung Ji Kim ◽  
Hyun Ho Jung ◽  
Won Seok Chang ◽  
Hyun Seok Choi ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Focused Ultrasound ◽  
Tumor Resection ◽  
Chemotherapeutic Agents ◽  
Brain Barrier ◽  
Clinical Trial Registration ◽  
Blood Brain ◽  
Chemotherapy Protocol ◽  
Multiple Blood

OBJECTIVEGlioblastoma (GBM) remains fatal due to the blood-brain barrier (BBB), which interferes with the delivery of chemotherapeutic agents. The purpose of this study was to evaluate the safety and feasibility of repeated disruption of the BBB (BBBD) with MR-guided focused ultrasound (MRgFUS) in patients with GBM during standard adjuvant temozolomide (TMZ) chemotherapy.METHODSThis study was a prospective, single-center, single-arm study. BBBD with MRgFUS was performed adjacent to the tumor resection margin on the 1st or 2nd day of the adjuvant TMZ chemotherapy at the same targets for 6 cycles. T2*-weighted/gradient echo (GRE) MRI was performed immediately after every sonication trial, and comprehensive MRI was performed at the completion of all sonication sessions. Radiological, laboratory, and clinical evaluations were performed 2 days before each planned BBBD.RESULTSFrom September 2018, 6 patients underwent 145 BBBD trials at various locations in the brain. The authors observed gadolinium-enhancing spots at the site of BBBD on T1-weighted MRI in 131 trials (90.3%) and 93 trials (64.1%) showed similar spots on T2*-weighted/GRE MRI. When the 2 sequences were combined, BBBD was observed in 134 targets (92.4%). The spots disappeared on follow-up MRI. There were no imaging changes related to BBBD and no clinical adverse effects during the 6 cycles.CONCLUSIONSThis study is the first in which repetitive MRgFUS was performed at the same targets with a standard chemotherapy protocol for malignant brain tumor. BBBD with MRgFUS was performed accurately, repeatedly, and safely. Although a longer follow-up period is needed, this study allows for the possibility of other therapeutic agents that previously could not be used due to the BBB.Clinical trial registration no.: NCT03712293 (clinicaltrials.gov)

Blood-brain barrier disruption in immature Fischer 344 rats

1984 ◽  
Vol 60 (4) ◽  
pp. 743-750 ◽  
Author(s):  
Dennis E. Bullard ◽  
Darell D. Bigner
Keyword(s):  
Blood Brain Barrier ◽  
Small Animal ◽  
Chemotherapeutic Agents ◽  
Brain Barrier ◽  
External Carotid ◽  
Blue Dye ◽  
Fischer 344 Rats ◽  
Content Type ◽  
Fischer 344 ◽  
Blood Brain

✓ Methods for transiently disrupting the blood-brain barrier (BBB) which are consistent with survival are described for immature Fischer 344 rats weighing 40 to 99 gm. A catheter was retrogradely inserted into the external carotid artery to the level of the bifurcation. Perfusion of 1.4 M mannitol or 1.6 M arabinose, at a rate of 0.01 to 0.1 ml/sec for 30 seconds, resulted in transient BBB disruption as measured by Evans blue dye (EBD) staining. Higher flow rates or perfusion with 10% to 30% dimethyl sulfoxide were associated with a mortality rate ranging from 0% to 44%. Perfusion with 0.9% sodium chloride or intrafemoral artery perfusion with 1.4 M mannitol did not disrupt the BBB. Optimum BBB disruption as measured by EBD staining was achieved with 1.6 M arabinose at 0.026 ml/sec for 30 seconds, at which time all of the 42 experimental animals had BBB disruption; all of the animals so treated survived 2 weeks following perfusion. This technique will allow the efficacy of delivering chemotherapeutic agents following BBB disruption to be tested in several of the more commonly used small-animal models for brain-tumor research.

HER-2/neu expression in glioblastoma multiforme (GBM)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e13035-e13035
Author(s):  
S. Gupta ◽  
H. Sheikh ◽  
C. Schneider ◽  
X. Zhang ◽  
A. Padmanabhan ◽  
...  
Keyword(s):  
Glioblastoma Multiforme ◽  
Tumor Cells ◽  
Blood Brain Barrier ◽  
Malignant Gliomas ◽  
Human Tumor ◽  
Brain Barrier ◽  
Breast Cancer Patients ◽  
Over Expression ◽  
Blood Brain ◽  
Her 2

e13035 Background: Glioblastoma multiforme (GBM) is a disease in which very few cytotoxic chemotherapy agents have been shown to have activity. This is partly due to their inability to cross the blood brain barrier. Trials with bevacizumab, a VEGF inhibitor that disrupts tumor angiogenesis, have demonstrated activity against this otherwise chemotherapy resistant disease. This has led to interest in other biologic agents that target angiogenic pathways for the treatment of GBM. Over-expression of HER-2/neu by human tumor cells is closely associated with increased angiogenesis and expression of VEGF. Lapatinib is a recently available low molecular weight immunotherapeutic agent that targets HER-2/neu proteins. In a recent study, breast cancer patients treated with lapatinib and capcitabine had decreased brain metastases indicating that lapatinib may cross the blood brain barrier and thus have potential in the treatment of malignant gliomas. Limited studies have evaluated HER-2/neu gene expression in GBM and the results are inconsistent. We evaluated the expression of Her-2/neu protein in 41 consecutive GBM cases to explore the potential utility of targeting this pathway. Methods: Archival histopathologic sections from 41 patients (age 26–89 years) with a diagnosis of GBM from 2004–2008 were reviewed. The diagnosis was confirmed and optimal sections were selected. Immunohistochemistry was performed on formalin-fixed, paraffin-embedded tissue sections using the primary antibody against HER-2/neu (clone 4B5, Ventana). The results were evaluated by three independent investigators. Interpretation was performed using the semi-quantitative criteria (Score 0 to 3+) currently used for primary breast carcinomas. Results: 38 out of 41 cases showed no immunohistochemical staining with HER-2/neu antibody (score 0). Three cases demonstrated weak, incomplete membrane staining of rare tumor cells (score 1+) and were interpreted as negative. The positive and negative controls worked properly. Conclusions: Our study indicates that there is no significant immunohistochemical over-expression of HER-2/neu protein in GBM. This suggests that HER-2/neu over-expression is not a significant oncogenic pathway in GBM, and therefore may not be a potential therapeutic target in this disease. No significant financial relationships to disclose.

Neurotoxicity of chemotherapeutic agents after blood-brain barrier modification: Neuropathological studies

1983 ◽  
Vol 14 (3) ◽  
pp. 316-324 ◽  
Author(s):  
Edward A. Neuwelt ◽  
Mark Glasberg ◽  
Eugene Frenkel ◽  
Peggy Barnett
Keyword(s):  
Blood Brain Barrier ◽  
Chemotherapeutic Agents ◽  
Brain Barrier ◽  
Blood Brain

scholarly journals Comparison of blood-brain barrier permeability in mice and rats using in situ brain perfusion technique

2000 ◽  
Vol 279 (3) ◽  
pp. H1022-H1028 ◽  
Author(s):  
Hideyasu Murakami ◽  
Hitomi Takanaga ◽  
Hirotami Matsuo ◽  
Hisakazu Ohtani ◽  
Yasufumi Sawada
Keyword(s):  
Blood Brain Barrier ◽  
Brain Perfusion ◽  
External Carotid Artery ◽  
Brain Barrier ◽  
External Carotid ◽  
Perfusion Technique ◽  
Perfusion Rate ◽  
In Situ Brain Perfusion ◽  
Blood Brain

Here we present a method for measuring the permeability coefficient-surface area product ( PS) values at the blood-brain barrier in mice, using the in situ brain perfusion technique originally developed for rats by Takasato et al. ( Am J Physiol Heart Circ Physiol 247: H484–H493, 1984). Retrograde infusion into the right external carotid artery increased the carotid perfusion pressure in proportion to the perfusion rate. Intravascular volume and cerebral perfusion fluid flow at a perfusion rate of 1.0 ml/min in mice were similar to those in rats. In addition, the contribution of systemic blood to total flow in the hemisphere was small (only 3.2%). These findings indicated that this perfusion rate is suitable for mice. The PS values of more than 20 different compounds were determined in mice by using the in situ brain perfusion technique, and comparisons were made with data from rats. There was a close relationship (1:1) between the PS values in mice and rats, indicating that brain capillary permeabilities are similar in mice and rats.

Simulation of Magnetic Nanoparticles Crossing through a simplified Blood-Brain Barrier model for Glioblastoma Multiforme Treatment

2021 ◽  
pp. 106477
Author(s):  
Apostolos A. Gkountas ◽  
Nickolas D. Polychronopoulos ◽  
George N. Sofiadis ◽  
Evangelos G. Karvelas ◽  
Leonidas A. Spyrou ◽  
...  
Keyword(s):  
Magnetic Nanoparticles ◽  
Glioblastoma Multiforme ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Blood Brain ◽  
Blood Brain Barrier Model ◽  
Barrier Model

Non-invasive transferrin targeted nanovesicles sensitize resistant glioblastoma multiforme tumors and improve survival in orthotopic mouse models

Nanoscale ◽  
2021 ◽  
Author(s):  
Puja Sandbhor ◽  
Jayant Goda ◽  
Bhabani Mohanty ◽  
Pradip Chaudhari ◽  
Shilpee Dutt ◽  
...  
Keyword(s):  
Glioblastoma Multiforme ◽  
Clinical Outcomes ◽  
Blood Brain Barrier ◽  
Mouse Models ◽  
Tumor Heterogeneity ◽  
Brain Barrier ◽  
Therapeutic Regimen ◽  
Non Invasive ◽  
Blood Brain

The blood–brain barrier (BBB) and tumor heterogeneity have resulted in abysmally poor clinical outcomes in glioblastoma (GBM) with the standard therapeutic regimen.

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