Growth of precultured human glioma biopsy specimens in nude rat brain

1999 ◽  
Vol 90 (1) ◽  
pp. 125-132 ◽  
Author(s):  
Olav Engebraaten ◽  
Geir Olav Hjortland ◽  
Henry Hirschberg ◽  
Øystein Fodstad
Keyword(s):  
Animal Model ◽  
Brain Tumor ◽  
Single Cells ◽  
Experimental Studies ◽  
In Vivo Model ◽  
Tumor Spheroids ◽  
Tumor Biopsy ◽  
Content Type ◽  
Biopsy Specimens ◽  
Fine Print

Object. The aim of this study was to develop an improved animal model for brain tumor study. The need for better and more relevant brain tumor models is generally acknowledged. Glioma tissue can be cultured directly from the biopsy specimen as tumor spheroids. Using such precultured tissue, a new in vivo model for studying human gliomas was established.Methods. Precultured small tumor spheroids (< 300 µm) prepared from cell lines or tumor biopsy fragments were injected into the brains of immunodeficient rats by using a 5-µl Hamilton syringe that had a piston in the needle. Tumors could be established by injecting a single spheroid derived from the U-87MG cell line, whereas inoculation of 10 spheroids resulted in a tumor take comparable to that attained with injection of 106 single cells. Biopsy specimens obtained from six patients who underwent surgery for glioblastoma multiforme were cultured as organotypic spheroids for 11 to 18 days before inoculation into the rats. The animals were killed 3 months after spheroid implantation. Microscopic examination revealed tumor growth in 87.5 to 100% of the animals inoculated with tumor spheroids from all but one of the tumor biopsy specimens. Extensive invasion and cell migration along the nerve tracts of the corpus callosum was found in tumors that originated from four of the six biopsy specimens.Conclusions. This approach, in which spheroids from precultured biopsy specimens are injected into the brains of immunodeficient animals, provides new means for experimental studies of human malignant brain tumors in a clinically relevant animal model.

Stereotaxic device for polar approaches in orthogonal systems

1984 ◽  
Vol 61 (6) ◽  
pp. 1146-1147 ◽  
Author(s):  
Massimo Scerrati ◽  
Alessandro Fiorentino ◽  
Massimo Fiorentino ◽  
Pietro Pola
Keyword(s):  
Brain Tumor ◽  
Tumor Biopsy ◽  
Content Type ◽  
Safety And Reliability ◽  
Orthogonal Systems ◽  
Fine Print

✓ A special stereotaxic device is described which was conceived and built to integrate the peculiar orthogonal approach of the well known Talairach apparatus with a polar approach. The device is useful to reach small and deep-seated brain targets, particularly those located on or close to the midline. Its use in several different stereotaxic operations, such as thalamotomy, brain-tumor biopsy, or radiotherapy, proved its flexibility, safety, and reliability.

Dynamic determination of human glioma invasion in vitro

1998 ◽  
Vol 89 (3) ◽  
pp. 441-447 ◽  
Author(s):  
Svein J. T. Nygaard ◽  
Hans K. R. Haugland ◽  
Ole Didrik Laerum ◽  
Morten Lund-Johansen ◽  
Rolf Bjerkvig ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Tumor Cell ◽  
Brain Tissue ◽  
Normal Brain ◽  
Tumor Spheroids ◽  
Normal Brain Tissue ◽  
Content Type ◽  
Biopsy Specimens ◽  
Fine Print

Object. The goal of this study was to evaluate whether there is any relationship between survival of patients with brain tumor and tumor proliferation or tumor invasion in vitro. Methods. Samples of freshly resected brain tumors from 14 patients with glioblastoma multiforme (GBM) were directly grown as three-dimensional multicellular spheroids. The tumor spheroids were cocultured with fetal rat brain cell aggregates (BCAs), used to represent an organotypical normal brain tissue model. Before the coculture, the tumor spheroids and the BCAs were stained with two different carbocyanine dyes, 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindocarbocyanine perchlorate (DiI) and 3,3′-dioctadecycloxacarbocyanine perchlorate (DiO), respectively. During the coculture, confocal laser scanning microscopy allowed a sequential analysis of tumor cell invasion by visualizing dynamic aspects of the invasive process. Single cocultures were examined at three different time points (24, 48, and 96 hours). During the observation period there was a change in the structural morphology of the cocultures, with a progressive decrease in BCA volume. Furthermore, the scanning confocal micrographs revealed a bidirectional movement of tumor cells and normal cells into brain and tumor tissue, respectively. It is also shown that there is a considerable variation in the rate of BCA destruction in cocultures of glioma spheroids generated directly from biopsy specimens. This variation is seen both between spheroids generated from the same biopsy as well as between spheroids that are grown from different biopsy specimens. Cell proliferation measured by Ki-67 immunohistochemical analysis of biopsy samples obtained in the same patients revealed a correlation between tumor cell proliferation and tissue destruction of the BCAs, as determined by a reduction in BCA volume (p = 0.0338). No correlation was found when survival was related to the same parameters (p > 0.05). Conclusions. The present work provides a model for quick and efficient assessment of dynamic interactions between tumor and normal brain tissue shortly after surgery.

A new rat model of chronic cerebral hypoperfusion associated with arteriovenous malformations

2002 ◽  
Vol 97 (5) ◽  
pp. 1198-1202 ◽  
Author(s):  
Jian Hai ◽  
Meixiu Ding ◽  
Zhilin Guo ◽  
Bingyu Wang
Keyword(s):  
Electron Microscopy ◽  
Animal Model ◽  
Arteriovenous Malformations ◽  
Perfusion Pressure ◽  
Chronic Cerebral Hypoperfusion ◽  
Cerebral Hypoperfusion ◽  
Model Group ◽  
Content Type ◽  
The Right ◽  
Fine Print

Object. A new experimental model of chronic cerebral hypoperfusion was developed to study the effects of systemic arterial shunting and obstruction of the primary vessel that drains intracranial venous blood on cerebral perfusion pressure (CPP), as well as cerebral pathological changes during restoration of normal perfusion pressure. Methods. Twenty-four Sprague—Dawley rats were randomly assigned to either a sham-operated group, an arteriovenous fistula (AVF) group, or a model group (eight rats each). The animal model was readied by creating a fistula through an end-to-side anastomosis between the right distal external jugular vein (EJV) and the ispilateral common carotid artery (CCA), followed by ligation of the left vein draining the transverse sinus and bilateral external carotid arteries. Systemic mean arterial pressure (MAP), draining vein pressure (DVP), and CPP were monitored and compared among the three groups preoperatively, immediately postoperatively, and again 90 days later. Following occlusion of the fistula after a 90-day interval, blood—brain barrier (BBB) disruption and water content in the right cortical tissues of the middle cerebral artery territory were confirmed and also quantified with transmission electron microscopy. Formation of a fistula resulted in significant decreases in MAP and CPP, and a significant increase in DVP in the AVF and model groups. Ninety days later, there were still significant increases in DVP and decreases in CPP in the model group compared with the other groups (p < 0.05). Damage to the BBB and brain edema were noted in animals in the model group during restoration of normal perfusion pressure by occlusion of the fistula. Electron microscopy studies revealed cerebral vasogenic edema and/or hemorrhage in various amounts, which correlated with absent astrocytic foot processes surrounding some cerebral capillaries. Conclusions. The results demonstrated that an end-to-side anastomosis between the distal EJV and CCA can induce a decrease in CPP, whereas a further chronic state of cerebral hypoperfusion may be caused by venous outflow restriction, which is associated with perfusion pressure breakthrough. This animal model conforms to the basic hemodynamic characteristics of human cerebral arteriovenous malformations.

Invasion of human glioma biopsy specimens in cultures of rodent brain slices: a quantitative analysis

2002 ◽  
Vol 97 (1) ◽  
pp. 169-176 ◽  
Author(s):  
Sophie de Boüard ◽  
Christo Christov ◽  
Jean-Sébastien Guillamo ◽  
Lina Kassar-Duchossoy ◽  
Stéphane Palfi ◽  
...  
Keyword(s):  
Cell Lines ◽  
Brain Slices ◽  
Lower Grade ◽  
Human Glioma ◽  
Newborn Mice ◽  
Content Type ◽  
Biopsy Specimens ◽  
Rodent Brain ◽  
Fine Print

Object. The reliable assessment of the invasiveness of gliomas in vitro has proved elusive, because most invasion assays inadequately model in vivo invasion in its complexity. Recently, organotypical brain cultures were successfully used in short-term invasion studies on glioma cell lines. In this paper the authors report that the invasiveness of human glioma biopsy specimens directly implanted into rodent brain slices by using the intraslice implantation system (ISIS) can be quantified with precision. The model was first validated by the demonstration that, in long-term studies, established glioma cells survive in the ISIS and follow pathways of invasion similar to those in vivo. Methods. Brain slices (400 µm thick) from newborn mice were maintained on millicell membranes for 15 days. Cells from two human and one rodent glioblastoma multiforme (GBM) cell lines injected into the ISIS were detected by immunohistochemistry or after transfection with green fluorescent protein—containing vectors. Preferential migration along blood vessels was identified using confocal and fluorescent microscopy. Freshly isolated (≤ 24 hours after removal) 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindocarbocyanine perchlorate—prelabeled human glioma biopsy specimens were successfully implanted in 19 (83%) of 23 cases, including 12 GBMs and seven lower grade gliomas (LGGs). Morphometric quantification of distance and density of tumor cell invasion showed that the GBMs were two to four times more invasive than the LGGs. Heterogeneity of invasion was also observed among GBMs and LGGs. Directly implanted glioma fragments were more invasive than spheroids derived from the same biopsy specimen. Conclusions. The ISIS combines a high success rate, technical simplicity, and detailed quantitative measurements and may, therefore, be used to study the invasiveness of biopsy specimens of gliomas of different grades.

Glioblastoma multiforme at the site of metal splinter injury: a coincidence?

1999 ◽  
Vol 91 (6) ◽  
pp. 1041-1044 ◽  
Author(s):  
Michael Sabel ◽  
Jörg Felsberg ◽  
Martina Messing-Jünger ◽  
Eva Neuen-Jacob ◽  
Jürgen Piek
Keyword(s):  
Brain Tumor ◽  
Glioblastoma Multiforme ◽  
Malignant Glioma ◽  
Causal Relationship ◽  
Propionibacterium Acnes ◽  
Glioma Tissue ◽  
Left Frontal Lobe ◽  
Content Type ◽  
Chronic Abscess ◽  
Fine Print

✓ The authors report the case of a man who had suffered a penetrating metal splinter injury to the left frontal lobe at 18 years of age. Thirty-seven years later the patient developed a left-sided frontal tumor at the precise site of the meningocerebral scar and posttraumatic defect. Histological examination confirmed a glioblastoma multiforme adjacent to the dural scar and metal splinters. In addition, a chronic abscess from which Propionibacterium acnes was isolated was found within the glioma tissue. The temporal and local association of metal splinter injury with chronic abscess, scar formation, and malignant glioma is highly suggestive of a causal relationship between trauma and the development of a malignant brain tumor.

Toward an agreement on terminology of nuclear and subnuclear divisions of the motor thalamus

1997 ◽  
Vol 86 (4) ◽  
pp. 670-685 ◽  
Author(s):  
Giorgio Macchi ◽  
Edward G. Jones
Keyword(s):  
Nonhuman Primates ◽  
Experimental Studies ◽  
Medial Lemniscus ◽  
Nuclear Mass ◽  
Content Type ◽  
Human Thalamus ◽  
Human Motor ◽  
Motor Thalamus ◽  
Fine Print ◽  
Somatosensory Areas

✓ The nomenclature most commonly applied to the motor-related nuclei of the human thalamus differs substantially from that applied to the thalamus of other primates, from which most knowledge of input—output connections is derived. Knowledge of these connections in the human is a prerequisite for stereotactic neurosurgical approaches designed to alleviate movement disorders by the placement of lesions in specific nuclei. Transfer to humans of connectional information derived from experimental studies in nonhuman primates requires agreement about the equivalence of nuclei in the different species, and dialogue between experimentalists and neurosurgeons would be facilitated by the use of a common nomenclature. In this review, the authors compare the different nomenclatures and review the cyto- and chemoarchitecture of the nuclei in the anterolateral aspect of the ventral nuclear mass in humans and monkeys, suggest which nuclei are equivalent, and propose a common terminology. On this basis, it is possible to identify the nuclei of the human motor thalamus that transfer information from the substantia nigra, globus pallidus, cerebellum, and proprioceptive components of the medial lemniscus to prefrontal, premotor, motor, and somatosensory areas of the cerebral cortex. It also becomes possible to suggest the principal functional systems involved in stereotactically guided thalamotomies and the functional basis of the symptoms observed following ischemic lesions in different parts of the human thalamus.

Frameless neuronavigation in intracranial endoscopic neurosurgery

2001 ◽  
Vol 94 (1) ◽  
pp. 72-79 ◽  
Author(s):  
Henry W. S. Schroeder ◽  
Wolfgang Wagner ◽  
Wolfgang Tschiltschke ◽  
Michael R. Gaab
Keyword(s):  
Third Ventricle ◽  
Colloid Cyst ◽  
Endoscopic Approach ◽  
Arachnoid Cysts ◽  
Tumor Biopsy ◽  
Foramen Of Monro ◽  
Endoscopic Neurosurgery ◽  
Content Type ◽  
Multiloculated Hydrocephalus ◽  
Fine Print

Object. Frameless computerized neuronavigation has been increasingly used in intracranial endoscopic neurosurgery. However, clear indications for the application of neuronavigation in neuroendoscopy have not yet been defined. The purpose of this study was to determine in which intracranial neuroendoscopic procedures frameless neuronavigation is necessary and really beneficial compared with a free-hand endoscopic approach. Methods. A frameless infrared-based computerized neuronavigation system was used in 44 patients who underwent intracranial endoscopic procedures, including 13 third ventriculostomies, nine aqueductoplasties, eight intraventricular tumor biopsy procedures or resections, six cystocisternostomies in arachnoid cysts, five colloid cyst removals, four septostomies in multiloculated hydrocephalus, four cystoventriculostomies in intraparenchymal cysts, two aqueductal stent placements, and fenestration of one pineal cyst and one cavum veli interpositi. All interventions were successfully accomplished. In all procedures, the navigational system guided the surgeons precisely to the target. Navigational tracking was helpful in entering small ventricles, in approaching the posterior third ventricle when the foramen of Monro was narrow, and in selecting the best approach to colloid cysts. Neuronavigation was essential in some cystic lesions lacking clear landmarks, such as intraparenchymal cysts or multiloculated hydrocephalus. Neuronavigation was not necessary in standard third ventriculostomies, tumor biopsy procedures, and large sylvian arachnoid cysts, or for approaching the posterior third ventricle when the foramen of Monro was enlarged. Conclusions. Frameless neuronavigation has proven to be accurate, reliable, and extremely useful in selected intracranial neuroendoscopic procedures. Image-guided neuroendoscopy improved the accuracy of the endoscopic approach and minimized brain trauma.

Metastases of glioblastoma multiforme to cervical lymph nodes

1973 ◽  
Vol 38 (5) ◽  
pp. 631-634 ◽  
Author(s):  
Sayed El-Gindi ◽  
Mamdouh Salama ◽  
Mokhtar El-Henawy ◽  
Said Farag
Keyword(s):  
Brain Tumor ◽  
Glioblastoma Multiforme ◽  
Lymph Nodes ◽  
Metastatic Lesion ◽  
Cervical Lymph Nodes ◽  
Content Type ◽  
The Brain ◽  
Fine Print

✓ Two cases of occipital glioblastoma multiforme are reported in which a metastatic lesion involving the cervical lymph nodes on the side of the previous craniotomy was verified during life. This suggests to the authors that the brain tumor metastasized via lymphatic channels.

Correlation of the relationships of brain—tumor interfaces, magnetic resonance imaging, and angiographic findings to predict cleavage of meningiomas

1999 ◽  
Vol 91 (3) ◽  
pp. 384-390 ◽  
Author(s):  
Faruk İldan ◽  
Metin Tuna ◽  
Alp İskender Göcer ◽  
Bülent Boyar ◽  
Hüseyin Bağdatoğlu ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Brain Tumor ◽  
Magnetic Resonance ◽  
Mr Imaging ◽  
Vascular Supply ◽  
Peritumoral Edema ◽  
Resonance Imaging ◽  
Content Type ◽  
Angiographic Findings ◽  
Fine Print

Object. The authors examined the relationships of brain—tumor interfaces, specific magnetic resonance (MR) imaging features, and angiographic findings in meningiomas to predict tumor cleavage and difficulty of resection.Methods. Magnetic resonance imaging studies, angiographic data, operative reports, clinical data, and histopathological findings were examined retrospectively in this series, which included 126 patients with intracranial meningiomas who underwent operations in which microsurgical techniques were used. The authors have identified three kinds of brain—tumor interfaces characterized by various difficulties in microsurgical dissection: smooth type, intermediate type, and invasive type. The signal intensity on T1-weighted MR images was very similar regardless of the type of brain—tumor interface (p > 0.1). However, on T2-weighted images the different interfaces seemed to correlate very precisely with the signal intensity and the amount of peritumoral edema (p < 0.01), allowing the prediction of microsurgical effort required during surgery. On angiographic studies, the pial—cortical arterial supply was seen to participate almost equally with the meningeal—dural arterial supply in vascularizing the tumor in 57.9% of patients. Meningiomas demonstrating hypervascularization on angiography, particularly those fed by the pial—cortical arteries, exhibited significantly more severe edema compared with those supplied only from meningeal arteries (p < 0.01). Indeed, a positive correlation was found between the vascular supply from pial—cortical arteries and the type of cleavage (p < 0.05).Conclusions. In this analysis the authors proved that there is a strong correlation between the amount of peritumoral edema, hyperintensity of the tumor on T2-weighted images, cortical penetration, vascular supply from pial—cortical arteries, and cleavage of the meningioma. Therefore, the consequent difficulty of microsurgical dissection can be predicted preoperatively by analyzing MR imaging and angiographic studies.

Pharmacokinetics of intracarotid artery 14C-BCNU in the squirrel monkey

1978 ◽  
Vol 48 (4) ◽  
pp. 587-593 ◽  
Author(s):  
Victor A. Levin ◽  
Pokar M. Kabra ◽  
Mary A. Freeman-Dove
Keyword(s):  
Brain Tumor ◽  
Brain Regions ◽  
Squirrel Monkeys ◽  
Intravenous Route ◽  
Content Type ◽  
Drug Levels ◽  
Drug Products ◽  
Bound Drug ◽  
Fine Print ◽  
Made In

✓ A comparison of intravenous to intracarotid artery (ICA) administration of 14C-BCNU (1,3-bis(2-chloroethyl)-1-nitrosourea) was made in squirrel monkeys. Radioactivity was measured as soluble drug products and as RNA-, DNA-, and protein-bound radioactivity. The ICA administration of BCNU achieved 190% to 280% higher brain nucleic acid-bound drug levels than use of the intravenous route in the infused hemisphere and 130% to 280% higher levels than in the noninfused hemisphere. In addition, some brain regions directly subserved by the middle cerebral artery had bound drug levels four- to fivefold greater than those found in regions of noninfused brain. The data suggest that a need for BCNU dose reduction due to myelotoxicity may be an indication for ICA therapy in selected brain-tumor cases.

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