Intracranial injection of human meningioma cells in athymic mice: an orthotopic model for meningioma growth

2000 ◽  
Vol 92 (2) ◽  
pp. 306-314 ◽  
Author(s):  
Ian E. McCutcheon ◽  
Keith E. Friend ◽  
Tammy M. Gerdes ◽  
Bing-Mei Zhang ◽  
David M. Wildrick ◽  
...  

Object. Although human meningioma cells have been heterotopically implanted in nude mice, introducing these cells into intracranial locations seems more likely to reproduce normal patterns of tumor growth. To provide an orthotopic xenograft model of meningioma, the authors implanted a controlled quantity of meningioma cells at subdural and intracerebral sites in athymic mice.Methods. Malignant (one tumor), atypical (two tumors), or benign (three tumors) meningiomas were placed into primary cell cultures. Cells (106/10 µl) from these cultures and from an immortalized malignant meningioma cell line, IOMM-Lee, were injected with stereotactic guidance into the frontal white matter or subdural space of athymic mice. Survival curves were plotted for mice receiving tumor cells of each histological type and according to injection site. Other mice were killed at intervals and their heads were sectioned whole. Hematoxylin and eosin staining of these sections revealed the extent of tumor growth.Conclusions. The median length of survival for mice with malignant, atypical, or benign tumors was 19, 42, or longer than 84 days, respectively. Atypical and malignant tumors were invasive, but did not metastasize extracranially. Malignant tumors uniformly showed leptomeningeal dissemination and those implanted intracerebrally grew locally and spread noncontiguously to the ventricles, choroid plexus, convexities, and skull base. Tumors formed in only 50% of mice injected with benign meningioma cells, whereas injection of more aggressive cells was uniformly successful at tumor production. The three types of human meningiomas grown intracranially in athymic mice maintained their relative positions in the spectrum of malignancy. However, atypical meningiomas became more aggressive after xenografting and acquired malignant features, implying that there had been immune constraint in the original host. Tumor cells injected into brain parenchyma migrated to more optimal environments and grew best there. This model provides insights into the biology of meningiomas and may be useful for testing new therapies.

1993 ◽  
Vol 79 (6) ◽  
pp. 845-852 ◽  
Author(s):  
Alain Pierre-Kahn ◽  
Jean-François Hirsch ◽  
Mathieu Vinchon ◽  
Christine Payan ◽  
Christian Sainte-Rose ◽  
...  

A study was made of 75 children treated between 1970 and 1990, with partial, subtotal, or total removal of three intrinsic and 72 exophytic or surface brain-stem tumors. In all cases, the goal of surgery was to remove as much tumor as possible. Extent of removal was defined according to data obtained from postoperative computerized tomography or magnetic resonance imaging, and was considered partial when only a small amount of tumor was removed, subtotal when a few cubic millimeters of tumor was left, and total when no residual tumor was seen on postoperative radiological investigations. An ultrasonic aspirator was used for the 43 most recent operations. Among tumor removals without the aspirator, 24 (75%) were partial, eight (25%) subtotal, and none total; with the use of the aspirator, the number of partial removals decreased to 44.5% while that of subtotal and total removals increased to 32% and 23.5%, respectively. There were 69 gliomas (92%) and 47 benign tumors (62.6%). Forty-nine patients were irradiated postoperatively, and 14 of the 23 patients whose benign tumors were removed totally or subtotally did not undergo irradiation. This study showed that: 1) the overall prognosis of patients with malignant tumors was poor and was not improved by surgery; 2) the survival rate of those with benign tumors was significantly (p < 0.01) lower after partial removal than after total or subtotal removal (52% and 94%, respectively, at 5 years); 3) comparison of means and proportions (Student's and chi-squared tests) between benign and malignant tumors showed a significant difference relating to patient age (p < 0.03), peritumoral hypodensity (p < 0.001), and preoperative duration of symptoms (p < 0.001); 4) stepwise logistic regression analysis confirmed that two of these three variables were related to malignancy: namely, patient age at surgery (p < 0.03) and presence of peritumoral hypodensity (p < 0.001); and 5) routine postoperative irradiation was contraindicated after total or subtotal removal of benign tumors.


1998 ◽  
Vol 88 (5) ◽  
pp. 831-839 ◽  
Author(s):  
Bridget J. McCarthy ◽  
Faith G. Davis ◽  
Sally Freels ◽  
Tanya S. Surawicz ◽  
Denise M. Damek ◽  
...  

Object. To explore factors affecting the survival rate in patients with meningiomas, the authors used the National Cancer Data Base (NCDB), which includes tumors from approximately 1000 hospitals participating in the American College of Surgeons tumor registry program. Methods. Analysis included over 9000 cases diagnosed from 1985 to 1988 and 1990 to 1992. Survival estimates were computed and prognostic factors were identified using a proportional hazards model. The overall 5-year survival rate was 69% and it declined with patient age. This rate was 81% in patients aged 21 to 64 years and 56% for patients 65 years of age or older. When patients were grouped by the histological type of their tumors, those with benign tumors had an overall 5-year survival rate of 70%, whereas the overall 5-year survival rates in patients with atypical and malignant meningiomas were 75% and 55%, respectively. Prognostic factors for benign tumors included age at diagnosis, tumor size, whether treated surgically, hospital type, and radiation therapy; for malignant tumors, the prognostic factors included: age at diagnosis, whether treated surgically, and radiation therapy. These factors were statistically significant. The 5-year rate for recurrence of symptoms (regardless of the method of treatment) was 19.2% for those with benign tumors and 32.4% for those with malignant tumors. In patients whose benign tumor had been completely removed, the 5-year rate of tumor recurrence was 20.5%. Conclusions. Although not population-based, the NCDB has the potential for providing pertinent information regarding patient characteristics and methods of treatment for benign, as well as malignant, brain tumors.


2005 ◽  
Vol 103 (2) ◽  
pp. 206-209 ◽  
Author(s):  
William A. Friedman ◽  
Gregory J. Murad ◽  
Patrick Bradshaw ◽  
Robert J. Amdur ◽  
William M. Mendenhall ◽  
...  

Object. In this paper the authors review the results of a single-center experience in the use of linear accelerator (LINAC) surgery for radiosurgical treatment of meningiomas. Methods. A retrospective analysis of all patients treated with LINAC surgery for meningiomas between May 1989 and December 2001 was performed. All patients participated in follow-up review for a minimum of 2 years, and no patients were excluded. Two hundred ten patients were treated during the study interval. The actuarial local control rate for benign tumors was 100% at both 1 and 2 years, and 96% at 5 years. The actuarial local control rate for atypical tumors was 100% at 1 year, 92% at 2 years, and 77% at 5 years; and that for malignant tumors was 100% at both 1 and 2 years, and only 19% at 5 years. Of the 210 patients 13 (6.2%) experienced temporary radiation-induced complications, and only five (2.3%) experienced permanent complications. In all patients with a permanent complication the histological characteristics of the meningioma were malignant. Conclusions. Linear accelerator surgery produced high local control rates and very low rates of permanent morbidity in patients harboring benign meningiomas.


2004 ◽  
pp. 341-345
Author(s):  
Choong Jin Whang ◽  
Gi Taek Yee ◽  
Chan Young Choi ◽  
Moon-Jun Sohn ◽  
Dong Joon Lee

Object. The role of radiosurgery has become increasingly important in the treatment of intracranial lesions. In this study the authors evaluated the efficacy of the Novalis shaped beam radiosurgery system (dedicated linear accelerator) for various brain and spinal lesions. Methods. Between November 2000 and October 2003 the authors treated 356 cases of various intracranial and extracranial lesions with Novalis shaped beam radiosurgery. Of these 356 cases, 109 cases were followed for more than a 2-year period. Fifty patients underwent fractionated stereotactic radiosurgery. Twenty patients (40%) harbored benign tumors (two acoustic neuromas, seven meningiomas, five pituitary adenomas, four optic gliomas, and two craniopharyngiomas), 18 patients (36%) harbored malignant tumors (16 glioblastoma multiforme [GBM], and two metastases), and the others included five with brainstem gliomas, one chordoma, five gliomas, and one with an arteriovenous malformation (AVM). Eighteen of 20 patients with benign tumors had good tumor control. Of 59 patients treated with single-dose stereotactic radiosurgery, 24 had benign intracranial tumors (12 acoustic neuromas, 11 meningiomas, and one pituitary adenoma), 20 had malignant tumors (two GBMs and 18 metastases), and the others were eight AVMs, two glomus jugulare tumors, three lymphomas, one pineal tumor, and one spinal tumor. Conclusions. Stereotactic radiosurgery and fractionated stereotactic radiosurgery using the Novalis shaped beam radiosurgery system are effective and safe noninvasive treatment modalities for various intracranial and extracranial lesions.


2000 ◽  
Vol 92 (5) ◽  
pp. 832-840 ◽  
Author(s):  
Matthias Simon ◽  
Tjoung-Won Park ◽  
Sven Leuenroth ◽  
Volkmar H. J. Hans ◽  
Thomas Löning ◽  
...  

Object. In recent reports, 6 to 19% of meningiomas have been classified as atypical or anaplastic/malignant. Some atypical and anaplastic meningiomas appear to arise from benign tumors by progression. Telomerase activation has recently been associated with malignant progression of human tumors. The authors have investigated a series of benign, atypical, and anaplastic/malignant meningiomas for telomerase activity and expression of the telomerase catalytic subunit human telomerase reverse transcriptase (hTERT).Methods. A quantitative telomeric repeat amplification protocol was used to detect telomerase enzyme activity in seven (21%) of 34 benign, but in nine (75%) of 12 atypical and in seven (100%) of seven anaplastic/malignant meningiomas. Very high levels of telomerase activity were observed only in highly aggressive tumors. Messenger (m)RNA expression of the catalytic subunit hTERT was found in 11 (33%) of 33 benign, 12 (92%) of 13 atypical, and all seven anaplastic/malignant tumors. All telomerase-positive lesions were also positive for hTERT mRNA, whereas no telomerase activity was detected in six (21%) of 29 hTERT-positive tumors. This indicates that upregulation of hTERT is the rate-limiting step for telomerase activation in the majority of meningiomas. Expression of telomerase and hTERT was seen in all four tumors with gross brain invasion. All recurrent tumors or meningiomas recurring during follow up expressed hTERT.Conclusions. The results are consistent with a role for telomerase activation during the development of malignancy in meningiomas. Hence, expression of telomerase activity and hTERT might prove to be potentially useful markers for the evaluation of these tumors.


1986 ◽  
Vol 65 (2) ◽  
pp. 168-171 ◽  
Author(s):  
Bernardo Borovich ◽  
Yaffa Doron ◽  
Jacob Braun ◽  
Joseph N. Guilburd ◽  
Menashe Zaaroor ◽  
...  

check; Globular single meningiomas are generally regarded as benign tumors that can be completely removed. Nevertheless, after a total macroscopic resection including the insertion zone (Grade 1 operation according to Simpson's classification), the incidence of recurrence ranged from 9% to 14% at the 5-year follow-up review. The authors have shown that single meningiomas represent only the visible predominant growth in the midst of a wide neoplastic field in the dura mater. Regional multiplicity in meningiomas would thus seem to be the rule. With this in mind, the authors propose to divide recurrences after Grade 1 operations into 1) true local and 2) false regional. A local recurrence is defined as a regrowth within the limits of the previous dural flap. Regional recurrence is when new growth develops outside the previous craniotomy site; this should not be considered as a recurrence but as a new primary site. These regional recurrences might explain some unexpected late tumor growth occurring after a Grade 1 operation. Five illustrative cases in which regional recurrence was detected by computerized tomography are presented. The authors also propose to add a supplementary grade to Simpson's surgical grading: Grade 0. This operation would entail a wide resection of the dura around the attachment zone of the meningioma. The authors hope that with a Grade 0 operation the incidence of recurrence might be reduced.


1992 ◽  
Vol 76 (2) ◽  
pp. 198-206 ◽  
Author(s):  
Laligam N. Sekhar ◽  
Anil Nanda ◽  
Chandra N. Sen ◽  
Carl N. Snyderman ◽  
Ivo P. Janecka

✓ The extended frontal approach is a modification of the transbasal approach of Derome. The addition of a bilateral orbitofrontal or orbitofrontoethmoidal osteotomy improves the exposure of midline lesions of the anterior, middle, and posterior skull base, while minimizing the need for frontal lobe retraction. The authors present a 5-year experience with 49 patients operated on via the extended frontal approach. In seven patients, the extended frontal approach was used alone; in the remaining 42, it was combined with other skull base approaches. Highly malignant tumors were removed en bloc, whereas benign tumors and low-grade malignancies were removed either en bloc or piecemeal. Reconstruction was usually performed using fascia lata, a pericranial flap, and/or autologous fat. A temporalis muscle flap or a distant microvascular free flap was required for some patients. One patient died 1 month postoperatively due to superior mesenteric artery thrombosis. Three patients had postoperative infections, two had cerebrospinal fluid leaks requiring reoperation, and four had brain contusions or hematomas. All but two patients recovered to their preoperative functional level. After an average follow-up period of 26 months (range 6 to 56 months), 64% of patients with benign lesions, 64% of patients with low-grade malignancies, and 44% of patients with high-grade lesions were alive with no evidence of disease.


2004 ◽  
Vol 101 (Supplement3) ◽  
pp. 341-345 ◽  
Author(s):  
Choong Jin Whang ◽  
Gi Taek Yee ◽  
Chan Young Choi ◽  
Moon-Jun Sohn ◽  
Dong Joon Lee

Object. The role of radiosurgery has become increasingly important in the treatment of intracranial lesions. In this study the authors evaluated the efficacy of the Novalis shaped beam radiosurgery system (dedicated linear accelerator) for various brain and spinal lesions. Methods. Between November 2000 and October 2003 the authors treated 356 cases of various intracranial and extracranial lesions with Novalis shaped beam radiosurgery. Of these 356 cases, 109 cases were followed for more than a 2-year period. Fifty patients underwent fractionated stereotactic radiosurgery. Twenty patients (40%) harbored benign tumors (two acoustic neuromas, seven meningiomas, five pituitary adenomas, four optic gliomas, and two craniopharyngiomas), 18 patients (36%) harbored malignant tumors (16 glioblastoma multiforme [GBM], and two metastases), and the others included five with brainstem gliomas, one chordoma, five gliomas, and one with an arteriovenous malformation (AVM). Eighteen of 20 patients with benign tumors had good tumor control. Of 59 patients treated with single-dose stereotactic radiosurgery, 24 had benign intracranial tumors (12 acoustic neuromas, 11 meningiomas, and one pituitary adenoma), 20 had malignant tumors (two GBMs and 18 metastases), and the others were eight AVMs, two glomus jugulare tumors, three lymphomas, one pineal tumor, and one spinal tumor. Conclusions. Stereotactic radiosurgery and fractionated stereotactic radiosurgery using the Novalis shaped beam radiosurgery system are effective and safe noninvasive treatment modalities for various intracranial and extracranial lesions.


2000 ◽  
Vol 93 (supplement_3) ◽  
pp. 68-73 ◽  
Author(s):  
Pierre-Hugues Roche ◽  
Jean Régis ◽  
Henry Dufour ◽  
Henri-Dominique Fournier ◽  
Christine Delsanti ◽  
...  

Object. The authors sought to assess the functional tolerance and tumor control rate of cavernous sinus meningiomas treated by gamma knife radiosurgery (GKS). Methods. Between July 1992 and October 1998, 92 patients harboring benign cavernous sinus meningiomas underwent GKS. The present study is concerned with the first 80 consecutive patients (63 women and 17 men). Gamma knife radiosurgery was performed as an alternative to surgical removal in 50 cases and as an adjuvant to microsurgery in 30 cases. The mean patient age was 49 years (range 6–71 years). The mean tumor volume was 5.8 cm3 (range 0.9–18.6 cm3). On magnetic resonance (MR) imaging the tumor was confined in 66 cases and extensive in 14 cases. The mean prescription dose was 28 Gy (range 12–50 Gy), delivered with an average of eight isocenters (range two–18). The median peripheral isodose was 50% (range 30–70%). Patients were evaluated at 6 months, and at 1, 2, 3, 5, and 7 years after GKS. The median follow-up period was 30.5 months (range 12–79 months). Tumor stabilization after GKS was noted in 51 patients, tumor shrinkage in 25 patients, and enlargement in four patients requiring surgical removal in two cases. The 5-year actuarial progression-free survival was 92.8%. No new oculomotor deficit was observed. Among the 54 patients with oculomotor nerve deficits, 15 improved, eight recovered, and one worsened. Among the 13 patients with trigeminal neuralgia, one worsened (contemporary of tumor growing), five remained unchanged, four improved, and three recovered. In a patient with a remnant surrounding the optic nerve and preoperative low vision (3/10) the decision was to treat the lesion and deliberately sacrifice the residual visual acuity. Only one transient unexpected optic neuropathy has been observed. One case of delayed intracavernous carotid artery occlusion occurred 3 months after GKS, without permanent deficit. Another patient presented with partial complex seizures 18 months after GKS. All cases of tumor growth and neurological deficits observed after GKS occurred before the use of GammaPlan. Since the initiation of systematic use of stereotactic MR imaging and computer-assisted modern dose planning, no more side effects or cases of tumor growth have occurred. Conclusions. Gamma knife radiosurgery was found to be an effective low morbidity—related tool for the treatment of cavernous sinus meningioma. In a significant number of patients, oculomotor functional restoration was observed. The treatment appears to be an alternative to surgical removal of confined enclosed cavernous sinus meningioma and should be proposed as an adjuvant to surgery in case of extensive meningiomas.


1989 ◽  
Vol 70 (5) ◽  
pp. 728-731 ◽  
Author(s):  
Jesús Vaquero ◽  
Santiago Coca ◽  
Santiago Oya ◽  
Roberto Martínez ◽  
Josefa Ramiro ◽  
...  

✓ A monoclonal antibody against the surface marker IOT-10 of natural killer (NK) cells was used to investigate the presence of these cells in a series of 25 glioblastomas. In 40% of the tumors, IOT-10-positive NK cells were found in small numbers scattered among the tumor cells. The presence of IOT-10-positive NK cells was not related to the degree of lymphocytic infiltration in the tumor as demonstrated by hematoxylin and eosin staining, nor did it appear to influence the survival time of the patients studied.


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