Estrogen and progestin binding by cytosolic and nuclear fractions of human meningiomas

1985 ◽  
Vol 62 (5) ◽  
pp. 750-756 ◽  
Author(s):  
Robert L. Martuza ◽  
Douglas C. Miller ◽  
David T. MacLaughlin
Keyword(s):  
Control Mechanism ◽  
Hormonal Control ◽  
Binding Assays ◽  
Tissue Samples ◽  
Content Type ◽  
Cellular Density ◽  
Equilibrium Binding ◽  
Frozen Tissue ◽  
Human Meningiomas ◽  
Fine Print

✓ Frozen tissue samples were obtained from meningiomas in 42 patients. Both cytosolic and nuclear fractions were tested for estradiol and progestin binding using equilibrium binding assays. The results were correlated with the age of the patient and the histological type and cellular density of the tumor. Cytosolic estradiol binding was noted in 25 (60%) of 42 tumors, with eight (19%) of the 42 having levels over 10 femtomoles (fM)/mg protein. Nuclear estradiol binding was detected in 16 (57%) of 28 tumors, with six (21%) of the 28 having levels over 10 fM/mg protein. Cytosolic progestin binding was noted in 16 (73%) of 22 samples, with levels in nine (41%) of 22 being greater than 10 fM/mg protein. There was no correlation between the level of cytoplasmic progestin binding and either the level of cytoplasmic estradiol binding or the level of nuclear estradiol binding. In several specimens, levels of cytoplasmic progestin binding in excess of 100 fM/mg protein were found in tissues demonstrating little or no estradiol binding by either the nucleus or the cytosol. This discrepancy differs from the situation found in other hormonally responsive tissues such as breast or uterus, and suggests either a possible derangement of the normal cellular hormonal control mechanism or that the measured hormone binder is a molecule other than a classical hormone receptor.

Evidence for mitogen-associated protein kinase activation and transduction of mitogenic signals by platelet-derived growth factor in human meningioma cells

2001 ◽  
Vol 94 (2) ◽  
pp. 293-300 ◽  
Author(s):  
Mahlon D. Johnson ◽  
Ann Woodard ◽  
Paul Kim ◽  
Maria Frexes-Steed
Keyword(s):  
Growth Factor ◽  
Thymidine Incorporation ◽  
Platelet Derived Growth Factor ◽  
Mapk Phosphorylation ◽  
Content Type ◽  
Human Meningiomas ◽  
Β Receptor ◽  
Fine Print ◽  
Stimulation Of ◽  
Mitogenic Signals

Object. Coexpression of platelet-derived growth factor (PDGF)—BB and activated PDGF-β receptor in meningioma cells indicates that this cytokine may act as an autocrine or paracrine stimulant of meningioma growth. The intracellular events transducing signals from PDGF-β receptor tyrosine kinases are unknown. In this study the authors evaluated whether or not mitogen-activated protein kinases (MAPKs) are expressed in meningiomas, regulate their growth, and transduce mitogenic signals of PDGF-BB. Methods. Ten human meningioma tumors as well as cells cultured from two normal leptomeninges and 10 additional human meningiomas were evaluated using Western blot analysis to determine the presence of MAPK and phosphorylated (activated) MAPK. The effects of PD098059, a selective inhibitor of MAPK phosphorylation/activation, on proliferation of meningioma cells stimulated with 10% fetal bovine serum was also evaluated. Last, the authors evaluated whether PDGF-BB stimulation of meningioma cells was associated with activation of MAPK. Western blots of lysates from meningiomas and from cultured leptomeningeal and meningioma cells demonstrated MAPK and phosphorylated MAPK. Treatment with PD098059 produced a 52 to 84% (x = 69.8) loss in [3H]thymidine incorporation, which was associated with a partial or complete loss of phosphorylated MAPK after 3 days of treatment. The PDGF-BB produced a significant increase in [3H]thymidine incorporation and phosphorylation of MAPK at 1 and 3 days. Coadministration of PD098059 completely blocked PDGF-BB's stimulation of [3H]thymidine incorporation and cell proliferation concomitant with reduced MAPK phosphorylation. Conclusions. The findings indicate that MAPK is constitutively expressed in leptomeningeal and meningioma cells and transduces mitogenic signals of PDGF, contributing to the growth of human meningiomas.

Carotid control for intracranial aneurysms

1988 ◽  
Vol 69 (1) ◽  
pp. 142 ◽  
Author(s):  
Milton D. Heifetz
Keyword(s):  
Carotid Artery ◽  
Internal Carotid Artery ◽  
Intracranial Aneurysms ◽  
Internal Carotid ◽  
Control Mechanism ◽  
Content Type ◽  
Flexible Cable ◽  
Cervical Internal Carotid Artery ◽  
Fine Print

✓ A new clamp with a flexible cable control mechanism for temporary intraoperative occlusion of the cervical internal carotid artery is described.

Radiosurgery for growth hormone—producing pituitary adenomas

2000 ◽  
Vol 93 (supplement_3) ◽  
pp. 6-9 ◽  
Author(s):  
Nan Zhang ◽  
Li Pan ◽  
En Min Wang ◽  
Jia Zhong Dai ◽  
Bin Jiang Wang ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Blood Glucose ◽  
Gamma Knife ◽  
Pituitary Adenomas ◽  
Gamma Knife Radiosurgery ◽  
Hormonal Control ◽  
High Blood Glucose ◽  
Content Type ◽  
Hormone Levels ◽  
Fine Print

Object. The authors sought to evaluate the effect of gamma knife radiosurgery (GKS) on growth hormone (GH)—producing pituitary adenoma growth and endocrinological response. Methods. From 1993 to 1997, 79 patients with GH-producing pituitary adenomas were treated with GKS. Seventysix patients had acromegaly. Sixty-eight patients were treated with GKS as the primary procedure. The tumor margin was covered with a 50 to 90% isodose and the margin dose was 18 to 35 Gy (mean 31.3 Gy). The dose to the visual pathways was less than 10 Gy except in one case. Sixty-eight patients (86%) were followed for 6 to 52 months. Growth hormone levels declined with improvement in acromegaly in all cases in the first 6 months after GKS. Normalization of the hormone levels was achieved in 23 (40%) of 58 patients who had been followed for 12 months and in 96% of cases for more than 24 months (43 of 45), or more than 36 months (25 of 26), respectively. With the reduction of GH hormone levels, 12 of 21 patients with hyperglycemia regained a normal blood glucose level (p < 0.001). The tumor shrank in 30 (52%) of 58 patients who had been followed for 12 months (p < 0.01), 39 (87%) of 45 patients for more than 2 years (p = 0.02), and 24 (92%) of 26 patients for more than 36 months. In the remainder of patients tumor growth ceased. Conclusions. Gamma knife radiosurgery for GH-producing adenomas showed promising results both in hormonal control and tumor shrinkage. A margin dose of more than 30 Gy would seem to be effective in improving the clinical status, reducing high blood glucose levels, and normalizing hypertension.

Histopathological findings in a surgically resected thalamic cavernous hemangioma 1 year after 40-Gy irradiation

2005 ◽  
Vol 102 (Special_Supplement) ◽  
pp. 56-58 ◽  
Author(s):  
István Nyáry ◽  
Otto Major ◽  
Zoltán Hanzély ◽  
György T. Szeifert
Keyword(s):  
Histopathological Examination ◽  
Posterior Part ◽  
Radiation Energy ◽  
Scar Tissue ◽  
Tissue Samples ◽  
Content Type ◽  
Histopathological Findings ◽  
Fractionated Radiotherapy ◽  
Cavernous Hemangiomas ◽  
Fine Print

✓ Stereotactic radiosurgery is a controversial treatment modality in the management of cerebral cavernous hemangiomas (CHs), and results vary from center to center. Even the interpretation of treatment failure is controversial. It is suggested that the systematic pathological investigation of irradiated specimens could help to resolve the controversy. A hemorrhagic lesion in the posterior part of the thalamus had been diagnosed as a tumor and was treated with 40-Gy fractionated radiotherapy. One year after this treatment the case was reconsidered based on new imaging evidence, and the lesion was removed by conventional craniotomy. Histopathological examination revealed a CH with postirradiation changes. Compared with nonirradiated control CH tissue samples, there was endothelial cell destruction and marked fibrosis with scar tissue formation in the stroma of the treated lesion. The histopathological findings in this specimen were similar to those described in arteriovenous malformations after gamma knife surgery. The results of light microscopic investigations suggest that the ionizing effect of radiation energy evokes vascular and connective tissue stroma changes in CHs as well.

Transsphenoidal extracapsular approach to pituitary tumors

1986 ◽  
Vol 64 (1) ◽  
pp. 16-20 ◽  
Author(s):  
Nobuo Hashimoto ◽  
Hajime Handa ◽  
Tatsuhito Yamagami
Keyword(s):  
Pituitary Adenomas ◽  
Transsphenoidal Surgery ◽  
Pituitary Tumors ◽  
Hormonal Control ◽  
Arachnoid Membrane ◽  
Content Type ◽  
Tumor Capsule ◽  
Suprasellar Extension ◽  
Fine Print ◽  
Transsphenoidal Resection

✓ Two years' experience with an extracapsular transsphenoidal approach to pituitary adenomas is presented. Some pituitary tumors contain an inordinate amount of connective tissue that often makes transsphenoidal resection difficult. By opening the tumor capsule and adjacent arachnoid membrane, such tumors with suprasellar extension can be safely removed. In some cases of functioning adenoma, resection of the diaphragma sellae and adjacent arachnoid membrane results in hormonal control. Among 62 cases of transsphenoidal surgery for pituitary adenomas, eight cases required this procedure. The surgical procedure is described and the cases are summarized. The indication and limitations of this procedure are discussed.

Cerebral effects of isovolemic hemodilution with a hypertonic saline solution

1985 ◽  
Vol 63 (6) ◽  
pp. 944-948 ◽  
Author(s):  
Michael M. Todd ◽  
Concezione Tommasino ◽  
Suzanne Moore
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Specific Gravity ◽  
Hypertonic Saline ◽  
Normal Saline ◽  
Hypertonic Saline Solution ◽  
Tissue Samples ◽  
Isovolemic Hemodilution ◽  
Content Type ◽  
Fine Print

✓ In view of a growing interest in the resuscitative use of hypertonic saline solutions, the authors have examined the cerebral effects of isovolemic hemodilution carried out over 1 hour (hematocrit decreased from 40% to 20%, stable arterial and right arterial pressures), using a hypertonic lactated Ringer's solution (HT-LR:Na+ 252 mEq/liter, osmolality 480 mOsm/liter). Experiments were carried out in anesthetized ventilated rabbits. Measured variables included cerebral blood flow (using the H2 clearance method), intracranial pressure (ICP), the electroencephalogram, spinal cord and skeletal muscle water content (%H2O), and the specific gravity of small (10- to 30-mg) tissue samples taken from different areas of the left hemisphere (including the cortex, thalamus, internal capsule, and hippocampus). The changes produced by HT-LR were compared with those seen in both undiluted control animals and in rabbits hemodiluted with normal saline (Na+ 155 mEq/liter, osmolality 310 mOsm/liter). The results demonstrate that hemodilution with HT-LR leads to the expected increases in serum Na+ and osmolality (158 ± 6 mEq/liter and 320 ± 5 mOsm/kg, respectively, mean ± standard deviation) and that these were accompanied by reductions in the %H2O of all cerebral and extracerebral tissues, increases in the specific gravity of all tissue regions studied, and a decrease in ICP (1.9 ± 0.7 mm Hg). By contrast, rabbits with hemodilution by normal saline showed no changes in either %H2O or specific gravity, but had significant increases in ICP (3.3 ± 1.3 mm Hg). Cerebral blood flow increased in all animals hemodiluted with either HT-LR or normal saline by a combined average of +29 ml/100 gm/min. Although these studies were performed in neurologically normal animals, the combination of cerebral changes seen with HT-LR (cerebral dehydration, less peripheral edema, decreased ICP but with increased cerebral blood flow) suggests that this approach may have some advantages over the use of isotonic fluids, and may have some utility in the resuscitation of head-injured patients.

Expression of the JAK and STAT superfamilies in human meningiomas

1999 ◽  
Vol 91 (3) ◽  
pp. 440-446 ◽  
Author(s):  
Lorenzo Magrassi ◽  
Claudio De-Fraja ◽  
Luciano Conti ◽  
Giorgio Butti ◽  
Lodovico Infuso ◽  
...  
Keyword(s):  
Nuclear Translocation ◽  
Signal Transduction Pathway ◽  
Janus Kinase ◽  
Response To Treatment ◽  
Interferon Α ◽  
Content Type ◽  
Human Meningiomas ◽  
Fine Print

Object. The goal of this study was to investigate whether the janus kinase/signal transducer and activator of transcription (JAK/STAT) signal transduction pathway is present and active in meningiomas. The results of these investigations are important for all meningioma therapies that, similar to interferon-α-2B (IFNα-2B), depend on activation of this pathway for their effect. The authors were interested in evaluating the importance, if any, of the JAK/STAT pathway in the biology and therapy for these tumors.Methods. Total proteins were extracted from 17 meningioma samples and the levels of JAKs and STATs were determined by using Western blot analysis. Levels of these proteins in meningiomas were compared with those found in normal dura. The JAKs and STATs (with the exception of Jak3 and Tyk2) were present both in the dura and in the meningiomas studied. In tumors JAK and STAT levels were always significantly higher than those found in normal dura. Differences in relative levels were found when meningiomas were subdivided according to the current neuropathological criteria and the highest levels were found in transitional meningiomas. The authors also investigated, using tyrosine-phosphorylated Stat1 and Stat3 antibodies, whether STATs were activated in meningiomas and normal dura in vivo. Their results indicate that both Stat1 and Stat3 are phosphorylated in vivo in meningiomas and in the dura. Furthermore, in vitro experiments in which two independent short-term cultures obtained from freshly dissected meningioma samples were used indicated that Stat1 and Stat3 are phosphorylated in response to treatment with IFNα-2B. Exposure of meningioma cells to IFNα-2B leads to nuclear translocation of tyrosine-phosphorylated Stat1 and Stat3, as demonstrated by immunocytochemical analysis.Conclusions. The results of this study indicate that the JAK and STAT families of proteins are important effectors in brain tumors and support the idea that the effects of IFNα in vivo are direct and not mediated by the immune system. This suggests a role for modulation of STAT transcription factors in inhibiting meningioma cell proliferation.

Expression of matrix metalloproteinases 2 and 9 in meningiomas associated with different degrees of brain invasiveness and edema

2001 ◽  
Vol 95 (5) ◽  
pp. 839-844 ◽  
Author(s):  
Ann-Christin Sandberg Nordqvist ◽  
Hubert Smurawa ◽  
Tiit Mathiesen
Keyword(s):  
Matrix Metalloproteinases ◽  
Clear Correlation ◽  
Consecutive Series ◽  
Tissue Samples ◽  
Content Type ◽  
Brain Invasion ◽  
Group Iii ◽  
Tumor Invasiveness ◽  
Group I ◽  
Fine Print

Object. Meningiomas display clinical characteristics that vary from very benign to clearly malignant with rapid invasive growth and metastasis. Benign meningiomas differ in their invasiveness and concomitant edema. This study was undertaken to analyze the expression of matrix metalloproteinases 2 and 9 (MMP-2 and MMP-9, respectively) in meningiomas associated with different degrees of brain invasion and edema. Methods. Tissue samples from 16 meningiomas were selected according to tumor invasiveness from a consecutive series of patients. Samples were analyzed for expression of both MMP-2 and MMP-9 by using in situ hybridization. The meningiomas consisted of three types: Group I, benign meningiomas that did not interfere with the arachnoid plane and exhibited no edema; Group II, benign meningiomas that invaded the arachnoid plane and caused edema; and Group III, aggressive and malignant meningiomas that caused edema and displayed brain invasion. In all 16 tumors analyzed, MMP-2 mRNA was identified. Levels of expression of MMP-2 mRNA were similar in all samples, and no correlation with increasing tumor invasiveness or associated edema could be detected. Expression of MMP-9 mRNA was identified in 14 of the 16 tumors, and a clear correlation with increasing tumor invasion into the brain was noted. Conclusions. Meningiomas express both MMP-2 and MMP-9. Tumor invasiveness, which ranged from minor with respect to the arachnoid membrane and progressed to frank brain invasion, correlated with the extent of MMP-9 expression. The findings indicate that MMP-9 expression and brain invasion are relevant mechanisms that must be interfered with in the treatment of aggressive and malignant meningiomas. No such correlation with MMP-2 was found.

Vascular extracellular matrix remodeling in cerebral aneurysms

1998 ◽  
Vol 89 (3) ◽  
pp. 431-440 ◽  
Author(s):  
Gerard Bruno ◽  
Roxanne Todor ◽  
Isabel Lewis ◽  
Douglas Chyatte
Keyword(s):  
Extracellular Matrix ◽  
Cerebral Aneurysms ◽  
Tissue Type ◽  
Extracellular Matrix Remodeling ◽  
Matrix Remodeling ◽  
Tissue Samples ◽  
Content Type ◽  
Control Tissue ◽  
Basilar Arteries ◽  
Fine Print

Object. The occurrence of cerebral aneurysms has been linked to alterations in the extracellular matrix and to matrix-degrading proteases. The purpose of the present study was to determine whether active extracellular matrix remodeling occurs within cerebral aneurysms. Methods. Aneurysm tissue was collected from 23 patients (two of whom had a ruptured aneurysm and 21 of whom had an unruptured aneurysm) and compared with 11 control basilar arteries harvested at autopsy. Active proteinases capable of gelatin lysis were identified by performing in situ zymography in the presence and absence of a metalloproteinase inhibitor (ethylenediamine tetraacetic acid) and a serine proteinase inhibitor (phenylmethylsulfonyl fluoride). Immunohistochemical analysis was used to localize plasmin, tissue-type (t)—plasminogen activator (PA), urokinase-type (u)—PA, membranetype (MT1)—matrix metalloproteinase (MMP), MMP-2, MMP-9, and tenascin. Focal areas of gelatin lysis occurred in most cerebral aneurysm tissue samples (17 of 21), but rarely in control arteries (two of 11) (p = 0.002). Both serine proteinases and MMPs contributed to gelatin lysis; however, the MMPs were the predominant enzyme family. Plasmin (p = 0.04) and MT1-MMP (p = 0.04) were expressed in the aneurysm tissue but were unusual in control tissue. The MMP-2 was also expressed more commonly in aneurysm than in control tissue (p = 0.07). The MMP-9 and t-PA were expressed in both groups; however, different staining patterns were observed between aneurysm and control tissue. Tenascin staining was commonly present in both groups, whereas u-PA staining was rarely present. Conclusions. Aneurysm tissue demonstrates increased proteolytic activity capable of lysing gelatin and increased expression of plasmin, MT1-MMP, and MMP-2 when compared with normal cerebral arteries. This activity may contribute to focal degradation of the vascular extracellular matrix and may be related to aneurysm formation and growth.

Vascular ultrastructure in human meningiomas and schwannomas

1973 ◽  
Vol 38 (4) ◽  
pp. 409-419 ◽  
Author(s):  
Don M. Long
Keyword(s):  
Electron Microscopy ◽  
Endothelial Cells ◽  
Endothelial Cell ◽  
Fluorescence Microscopy ◽  
Cell Junctions ◽  
Content Type ◽  
Cerebrovascular Permeability ◽  
Human Meningiomas ◽  
Fine Print

✓ Nineteen meningiomas and schwannomas have been studied by fluorescence microscopy and electron microscopy. Increased cerebrovascular permeability to protein was demonstrated in each tumor. The anatomical explanation for this increased permeability to protein was found in open endothelial cell junctions, gaps between endothelial cells, and fenestrations in capillary endothelial membranes.

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