Hormonal dependency of cerebral meningiomas

1990 ◽  
Vol 73 (5) ◽  
pp. 743-749 ◽  
Author(s):  
Uwe M. H. Schrell ◽  
Eric F. Adams ◽  
Rudolf Fahlbusch ◽  
Robert Greb ◽  
Gustav Jirikowski ◽  
...  
Keyword(s):  
Estrogen Receptors ◽  
Binding Sites ◽  
Solid Phase ◽  
Steroid Receptors ◽  
Progesterone Receptors ◽  
Nuclear Compartment ◽  
Content Type ◽  
High Affinity ◽  
Immunohistochemical Techniques ◽  
Fine Print

✓ Female sex steroid receptors were examined in 50 human cerebral meningiomas. For estrogen receptors, high-affinity binding sites (dissociation constant (Kd): 0.05 to 0.2 nM) were found in the cytosolic fraction with a capacity of less than 4 fmol/mg protein in 10 meningiomas using a dextran-coated charcoal (DCC) assay. In the same cytosolic fraction, the solid-phase enzyme immunoassay revealed only one cytosol with a positive colorimetric reaction equal to 5 fmol/mg protein. However, in the nuclear compartment, none of the tumors stained positively for estrogen receptors with immunohistochemical techniques. In addition, the most convincing evidence for the absence of estrogen receptors was obtained by in situ hybridization using an oligonucleotide probe complementary to a fraction of the human receptor messenger ribonucleic acid (mRNA). In none of the 50 meningiomas was the expression of estrogen mRNA coding for the estrogen receptor detected. For progesterone receptors, high-affinity binding sites (Kd: 0.3 to 2.6 nM) were found in 49 of the 50 tumors using a DCC assay. In the same cytosols, solid-phase enzyme immunoassay revealed that each tumor was positive for progesterone receptors. However, in the nuclear compartment, only five tumors had partially positive staining for progesterone receptors with immunohistochemical techniques. Within the confines of this study, it is concluded that: 1) the estrogen receptor is generally absent in meningioma tissue, and 2) the progesterone receptor is mainly absent in the nuclear compartment, leading to the conclusion that the cytosolic progesterone receptor may be an inactive form. This study suggests that female sex steroid receptors are not primarily involved in the proliferative rate of cerebral meningiomas and that they are of no current significance as markers for adjuvant medical therapy of most meningiomas.

Estrogen and Progesterone Receptors in Meningiomas: Comparison of Nuclear Binding, Dextran-Coated Charcoal, and Immunoperoxidase Staining Assays

Neurosurgery ◽  
1989 ◽  
Vol 25 (4) ◽  
pp. 546-553 ◽  
Author(s):  
Jaroslava Halper ◽  
Douglas S. Colvard ◽  
Bernd W. Scheithauer ◽  
Nai-Siang Jiang ◽  
Michael F. Press ◽  
...  
Keyword(s):  
Estrogen Receptors ◽  
Steroid Receptors ◽  
Progesterone Receptors ◽  
Immunoperoxidase Staining ◽  
Estrogen And Progesterone Receptors ◽  
High Affinity ◽  
Nuclear Binding ◽  
Dextran Coated Charcoal ◽  
The Status

Abstract We studied the status of estrogen (ER) and progesterone (PR) receptors in meningiomas removed from 52 patients, comparing dextran-coated charcoal (DCC), nuclear binding (NB), and immunoperoxidase (IP) assays. Each of the assays was performed independently by investigators well-experienced with these assays. The NB assay is a new assay that measures functional steroid receptors—that is, the activation of the receptor and its binding to the nucleus. The assay is very sensitive and requires a relatively small amount of tissue as compared with the DCC assay. In agreement with data from other studies, PR were detected in most meningiomas by all 3 methods: in 69% of the cases by NB, in 76% by DCC, and in 89% by IP. ER were detected in only a few cases: in 33% by NB, in 2% by DCC, and in none by the IP assay. The agreement for PR sites was 62% for all 3 assays, it was 66% between the NB and DCC assays, 67% between the NB and IP assays, and 86% between the DCC and IP assays. Of 26 cases that were positive by the DCC assay, 6 (23%) were negative by NB. The overall agreement for all three ER assays was 65%. The data suggest that the majority of meningiomas contain high-affinity receptors for progesterone, that estrogen receptors are present in only a few meningiomas, and that some of these estrogen and progesterone receptors appear to be functional.

Hormone receptors in initially excised versus recurrent intracranial meningiomas

1994 ◽  
Vol 81 (2) ◽  
pp. 184-187 ◽  
Author(s):  
Abraham B. Rubinstein ◽  
David Loven ◽  
Abraham Geier ◽  
Eli Reichenthal ◽  
Natan Gadoth
Keyword(s):  
Estrogen Receptors ◽  
Hormone Receptors ◽  
Progesterone Receptors ◽  
Hormone Treatment ◽  
Content Type ◽  
Intracranial Meningiomas ◽  
Tumor Group ◽  
Induced Tumors ◽  
Radiation Induced ◽  
Fine Print

✓ Intracranial meningiomas from 51 surgical patients consecutively treated during an 18-month period were evaluated for the presence of receptors to progesterone and estrogen. Thirty-eight patients underwent initial resection during this time and 13 underwent reoperation for recurrent disease. With positivity defined as receptor levels greater than 10 fmol/mg of cytosol protein, 84% of all the meningiomas were positive for progesterone receptors, whereas only 33% were positive for estrogen receptors. Among the recurrent meningiomas, 92% showed evidence of progesterone receptors and 54% of estrogen receptors; these figures were not significantly different from the corresponding incidence of 82% and 26%, respectively, among the initially excised tumors. However, the mean concentration of progesterone receptors in the recurrent tumor group was significantly higher when compared to the concentration in the initially excised group (p < 0.02). Twenty meningiomas (39%) were considered to be radiation-induced, since they were removed from patients who had received scalp irradiation during childhood. The incidence and concentration of receptors in the radiation-induced tumors were generally comparable to those in the spontaneous meningiomas. This study confirms previous reports of a high incidence of hormone receptors, mainly for progesterone, in meningiomas. In addition, it shows that in recurrent meningiomas these receptors persist and even increase. The results therefore support hormone treatment for nonresectable meningiomas, especially at recurrence.

Estrogen and progesterone receptors in meningiomas

1984 ◽  
Vol 60 (5) ◽  
pp. 985-993 ◽  
Author(s):  
David W. Cahill ◽  
Nasir Bashirelahi ◽  
Louis W. Solomon ◽  
Thomas Dalton ◽  
Michael Salcman ◽  
...  
Keyword(s):  
Menstrual Cycle ◽  
Gradient Centrifugation ◽  
Estrogen Therapy ◽  
Progesterone Receptors ◽  
The United States ◽  
Content Type ◽  
Therapeutic Implications ◽  
Exogenous Estrogen ◽  
French Group ◽  
Fine Print

✓ Two-thirds of all meningiomas and four-fifths of intraspinal and sphenoidal meningiomas occur in women. Meningiomas frequently enlarge or become symptomatic during pregnancy or during the luteal phase of the menstrual cycle. There is an increased incidence of meningiomas in women with breast carcinoma. In a series of 23 patients with meningiomas, the authors assayed biopsy specimens of the tumor for the presence of estrogen (ER) and progesterone (PR) receptors, using glycerol density gradient centrifugation and dextran-coated charcoal techniques. Significant levels of ER were found in only 17% of the patients, while significant PR levels were detected in 39%. Only one of the 16 tumors from female patients had significant ER levels, whereas three of the seven tumors from men had significant ER levels. Eight of the 16 tumors in women had significant PR levels, whereas only one of the seven tumors in men had a significant PR level. Thus, three out of four tumors with definite ER were from men, whereas eight of nine tumors with definite PR were from women. Of the eight women whose tumors contained PR, three were premenopausal and five postmenopausal. The single tumor with high levels of PR in the male patient was histologically atypical. The results of this series were compared with six published series of sex steroid assays in meningiomas. These seven series were divided into two groups: one group included two reports from the same laboratories in France, and the other the remaining five reports. Much higher percentages of both ER- and PR-positive tumors were reported from the French group. The authors suggest that this discrepancy may be due to the use of preoperative glucocorticoid therapy in the series from the United States. Since meningiomas are known to enlarge during periods when levels of circulating progestins are high, the presence of significant quantities of PR in a high percentage of tumors may have therapeutic implications for recurrent, malignant, or incompletely excised tumors, or for medically fragile patients. Conversely, since meningiomas are not known to enlarge during the proliferative phase of the menstrual cycle or with exogenous estrogen therapy, the small number of tumors positive for ER may indicate that ER lacks clinical significance. High levels of PR found in a small group of histologically aggressive tumors in several series may indicate that hormonal therapy may be especially useful in this difficult subset of patients.

Radiation-induced meningiomas: clinical, pathological, cytokinetic, and cytogenetic characteristics

2004 ◽  
Vol 100 (6) ◽  
pp. 1002-1013 ◽  
Author(s):  
Ossama Al-Mefty ◽  
Cahide Topsakal ◽  
Svetlana Pravdenkova ◽  
Jeffrey R. Sawyer ◽  
Michael J. Harrison
Keyword(s):  
Progesterone Receptors ◽  
Latency Period ◽  
Content Type ◽  
Chromosome 1P ◽  
Proliferation Indices ◽  
Cytogenetic Aberrations ◽  
Additional Chromosome ◽  
Radiation Induced ◽  
The Mean ◽  
Fine Print

Object. Radiation-induced meningiomas are known to occur after high- and low-dose cranial radiation therapy. The goal of this study was to discern the distinguishing findings and characteristics of radiation-induced meningiomas. Methods. The records of 16 patients (seven men and nine women) who fulfilled the criteria for radiation-induced meningiomas were retrospectively reviewed. Clinical, histopathological, cytokinetic, and cytogenetic findings as well as the patients' outcome were analyzed. The mean age of the patients was 38.8 years and the mean tumor latency was 26.5 years. Five patients had multiple meningiomas in the irradiated field. The recurrence rate was 100% after the initial resection; 62% of patients had a second recurrence and 17% had a third recurrence. Thirty-eight percent of patients had atypical or malignant histopathological findings. The presence of progesterone receptors and low proliferation indices in these patients did not correlate with benign tumor behavior. Cytogenetic analysis showed multiple clonal aberrations in all tumors studied. The most frequent aberrations were found on chromosomes 1p, 6q, and 22. Derivative, lost, or additional chromosome 1p was found in 89% of cases and loss or deletion on chromosome 6 was found in 67%. Conclusions. The age of patients at presentation with meningioma and the latency period of radiation-induced meningiomas are dose related. These tumors are more aggressive and are certain to recur, have a higher histopathological grade, and are associated with complex cytogenetic aberrations particularly involving 1p and 6q.

Immunocytochemical evidence of lymphocytic derivation of neoplastic cells in malignant angioendotheliomatosis

1991 ◽  
Vol 74 (5) ◽  
pp. 757-762 ◽  
Author(s):  
W. Craig Clark ◽  
F. Curtis Dohan ◽  
Timothy Moss ◽  
John B. Schweitzer
Keyword(s):  
Endothelial Cell Proliferation ◽  
Cell Of Origin ◽  
Content Type ◽  
Therapeutic Implications ◽  
Ulex Europaeus ◽  
Small Vessels ◽  
Immunohistochemical Techniques ◽  
Brain And Spinal Cord ◽  
The Brain ◽  
Fine Print

✓ Neoplastic angioendotheliomatosis is a rare disorder usually characterized by primarily cutaneous or neurological symptoms. Approximately 40 cases of malignant angioendotheliomatosis with primary central nervous system (CNS) symptoms have been reported. Some investigators have postulated a hematopoietic origin for this neoplasm. Most of the literature, however, has perpetuated the idea that the often bizarre symptoms seen with this entity result from neoplastic endothelial cell proliferation within the small vessels of affected organs, including the brain and spinal cord. This report describes the immunohistochemical examination and confirmation of the cell of origin of this neoplasm based on five previously unpublished cases of malignant angioendotheliomatosis with primarily CNS symptoms. It includes the first documentation of a T-cell lymphoma presenting as malignant angioendotheliomatosis. All cases include autopsy findings, and in four cases the diagnosis was made postmortem. One case was proven by stereotactic biopsy, but the patient succumbed as a result of severe intracranial bleeding that occurred at the time of biopsy. Tissues were studied with avidin-biotin peroxidase immunohistochemical techniques using a panel of monoclonal antibodies directed against the leukocyte common antigen, LN-1, LN-2, and anti-Factor VIII, and also using Ulex europaeus agglutinin 1. Based on the results obtained, the authors conclude that the proliferative cells seen within the vessel lumina are of lymphocytic origin and agree that the condition should more properly be designated intravascular lymphomatosis. The therapeutic implications of this conclusion point to the possible administration of chemotherapy and radiotherapy in an effort to achieve remissions in an otherwise relentlessly progressive neurological disorder.

Potent and specific killing of human malignant brain tumor cells by an anti-transferrin receptor antibody-ricin immunotoxin

1987 ◽  
Vol 66 (6) ◽  
pp. 850-861 ◽  
Author(s):  
John Zovickian ◽  
Virginia Gray Johnson ◽  
Richard J. Youle
Keyword(s):  
Tumor Cells ◽  
Transferrin Receptor ◽  
Solid Phase ◽  
Target Cells ◽  
Neoplastic Disease ◽  
Normal Brain ◽  
Plant Toxin ◽  
Content Type ◽  
Hybrid Molecules ◽  
Fine Print

✓ Immunotoxins are hybrid molecules which combine the exquisite selectivity of monoclonal antibodies with the potent toxicity of protein toxins. An immunotoxin was constructed by linking a murine monoclonal antibody against the human transferrin receptor (TR) to the plant toxin, ricin. The cytotoxic activity of the anti-TR-ricin immunotoxin was tested in vitro and demonstrated highly potent and cell type-specific killing of cells derived from human glioblastoma, medulloblastoma, and leukemia. The anti-TR-ricin immunotoxin killed more than 50% of “target” cells at a concentration of 5.6 × 10−13 M after an 18-hour incubation with the ionophore, monensin. This potency exceeds that of any other anti-TR immunotoxin reported in the literature. When the activity of the anti-TR-ricin immunotoxin against “target” tumor-derived cells was compared with the immunotoxin's activity against “non-target” cells, it could be predicted that a selective toxicity of anti-TR-ricin immunotoxin between tumor cells and normal brain was more than 150- to 1380-fold. Solid-phase indirect radioimmunoassay techniques were used to demonstrate significantly higher levels of TR in the glioblastoma- and medulloblastoma-derived cell lines, as well as in surgical tissue samples of medulloblastoma and glioblastoma, as compared to normal brain. Immunotoxins targeted to the TR may possess sufficient specificity to be of therapeutic importance, particularly to treat neoplastic disease of the central nervous system involving compartments (such as intrathecal, intraventricular, or cystic) where delivery of immunotoxins to tumor would not require transvascular transport.

Effect of the novel high-affinity glycine-site N-methyl-d-aspartate antagonist ACEA-1021 on 125I-MK-801 binding after subdural hematoma in the rat: an in vivo autoradiographic study

1996 ◽  
Vol 85 (4) ◽  
pp. 655-661 ◽  
Author(s):  
Xiao Di ◽  
Ross Bullock
Keyword(s):  
Nmda Receptor ◽  
Ion Channel ◽  
Subdural Hematoma ◽  
Nmda Antagonist ◽  
Channel Activation ◽  
Content Type ◽  
Mk 801 ◽  
High Affinity ◽  
Fine Print

✓ Acute subdural hematoma (SDH) complicates 20% of severe human head injuries and causes death or severe disability in 60% of these cases, due to brain swelling and high intracranial pressure. Although the mechanisms for these phenomena are unknown, previous studies have implicated excitatory amino acid—mediated mechanisms in both humans and animal models. The authors therefore performed in vivo autoradiography using 125I-MK-801, a high-affinity noncompetitive N-methyl-d-aspartate (NMDA) receptor antagonist, as a tracer to evaluate NMDA ion channel activation spatially and temporally as a factor causing cytotoxic swelling. Acute SDH was induced in 16 anesthetized rats using 0.4 ml autologous venous blood. Fifty microcuries of 125I-MK-801 was injected via an aortic arch cannula 30 minutes after onset of SDH. The effect of a new putatively neuroprotective drug, ACEA-1021, a glycine-specific binding site NMDA antagonist, on 125I-MK-801 binding was tested on five animals. “Nonspecific” 125I-MK-801 binding in the rat brain was assessed by pretreatment with “cold” (nonradiolabeled) MK-801 in five more animals. Four hours later the animals were sacrificed and brain sections were apposed to radiation-detecting high-sensitivity photographic film with precalibrated plastic standards for 4 weeks. A striking and highly significant 1.7- to 4.8-fold increase in 125I-MK-801 binding was seen in the penumbra of viable tissue surrounding the ischemic zone beneath the acute SDH, when compared to contralateral hemisphere binding (p < 0.001). The MK-801 pretreatment markedly reduced 125I-MK-801 uptake in this penumbral zone (4.73 ± 0.36 nCi/mg control vs. 2.85 ± 0.08 nCi/mg cold MK-801; p < 0.0001), indicating that the increased binding in the penumbra of the lesion was due to NMDA ion channel activation. Pretreatment with ACEA-1021 reduced 125I-MK-801 uptake by 28% (3.41 ± 0.26 nCi/mg vs. 4.73 ± 0.36 nCi/mg; p < 0.05), indicating that this agent prevents opening of the NMDA ion channel and, thus, exposure of its receptor for MK-801 binding. These studies show intense foci of penumbral NMDA receptor-mediated ion channel activation after onset of SDH, which is markedly reduced by an NMDA antagonist. Such agents are thus likely to reduce cell swelling after SDH occurs.

Benzodiazepine receptors and cerebrospinal fluid formation

1990 ◽  
Vol 72 (5) ◽  
pp. 759-762 ◽  
Author(s):  
Gregg L. Williams ◽  
Michael Pollay ◽  
Thomas Seale ◽  
Brent Hisey ◽  
P. Alex Roberts
Keyword(s):  
Cerebrospinal Fluid ◽  
Choroid Plexus ◽  
Binding Sites ◽  
Benzodiazepine Receptors ◽  
Secretory Activity ◽  
Assay Method ◽  
Content Type ◽  
High Affinity ◽  
Fluid Formation

✓ There is autoradiographic evidence that peripheral-type benzodiazepine ligands bind with high affinity to the membranes of choroid plexus tissue. In this study, the binding of a 4′-chloro analog of diazepam (Ro 5-4864) to rabbit choroid plexus and cerebral cortex was accomplished utilizing an in vitro radioactive assay method. A kinetic analysis of this binding revealed a relatively high affinity of this ligand (KD) for peripheral binding sites in plexus tissue (KD = 16.1 nM/mg protein). There was a 4.6-fold greater density of binding sites (total receptor density (Bmax) = 2.3 pmol/mg) in choroidal membrane as compared to cortical tissue (Bmax = 0.5 pmol/mg). In 40 rabbits in which a ventricular perfusion system was used, the rate of cerebrospinal fluid (CSF) formation was observed to decrease some 48% in the presence of 10−4 M Ro 5-4864, although some inhibition of secretory activity was still noted at a CSF concentration of 10−8 M. The choroid plexus tissue levels of adenosine 3′,5′cyclic monophosphate (cAMP) and adenosine triphosphatase (ATPase) were not affected by 10−4 M Ro 5-4864. The results of this study support the notion that the specific benzodiazepine peripheral binding sites in choroid plexus serve to modulate CSF formation. The mechanism of action is poorly understood but does not involve the transport ATPase system or the second messenger cAMP.

scholarly journals Peptide Scanning of SARS-CoV and SARS-CoV-2 Spike Protein Subunit 1 Reveals Potential Additional Receptor Binding Sites

2021 ◽  
Author(s):  
Weilin Lin ◽  
Jannatul Rafeya ◽  
Vanessa Roschewitz ◽  
David Smith ◽  
Adrian Keller ◽  
...  
Keyword(s):  
Receptor Binding ◽  
Binding Sites ◽  
Neutralizing Antibodies ◽  
Solid Phase ◽  
Solid Phase Peptide Synthesis ◽  
Spike Protein ◽  
Loss Of Function ◽  
Protein Subunit ◽  
Viral Attachment ◽  
High Affinity

The binding of SARS-CoV and SARS-CoV-2 to the ACE2 receptor on human cells is mediated by the spike protein subunit 1 (S1) on the virus surfaces, while the receptor binding domains (RBDs) of S1 are the major determinants for the interaction with ACE2 and dominant targets of neutralizing antibodies. However, at the virus-host interface, additional biomolecular interactions, although being relatively weak in affinity and low in specificity, could also contribute to viral attachment and play important roles in gain- or loss-of-function mutations. In this work, we performed a peptide scanning of the S1 domains of SARS-CoV and SARS-CoV-2 by synthesizing 972 16-mer native and mutated peptide fragments using a high throughput in situ array synthesis technology. By probing the array using fluorescently labelled ACE2, a number of previously unknown potential receptor binding sites of S1 have been revealed. 20 peptides were synthesized using solid phase peptide synthesis, in order to validate and quantify their binding to ACE2. Four ACE2-binding peptides were selected, to investigate whether they can be assembled through a biotinylated peptide/neutravidin system to achieve high affinity to ACE2. A number of constructs exhibited high affinity to ACE2 with Kd values of pM to low nM.

Quantitative imaging of estrogen and progesterone receptors, estrogen-regulated protein, and growth fraction: immunocytochemical assays in 52 meningiomas

1994 ◽  
Vol 81 (5) ◽  
pp. 765-773 ◽  
Author(s):  
Pablo Bouillot ◽  
Jean-François Pellissier ◽  
Benedicte Devictor ◽  
Noel Graziani ◽  
Nicole Bianco ◽  
...  
Keyword(s):  
Histological Grade ◽  
Quantitative Imaging ◽  
Progesterone Receptors ◽  
Clinicopathological Features ◽  
Growth Fraction ◽  
Low Grade ◽  
Cell Nuclei ◽  
Content Type ◽  
Immunocytochemical Assay ◽  
Fine Print

✓ Quantitative imaging of estrogen receptors (ER's), progesterone receptors (PR's), estrogen-regulated protein (pS2), and growth fraction (Ki67) immunocytochemical assays were performed in 52 meningiomas. The results were correlated with clinical (age, sex, hormonal status, and tumor volume and location) and morphological (histological types and grades) data. The authors observed a lack of ER's in all meningiomas but the presence of PR's in 53% of these meningiomas. The immunoreactivity was restricted to tumor cell nuclei. The PR immunocytochemical assay was correlated with tumor location, histological type, histological grade, and pS2 immunocytochemical assay, but not with Ki67 immunocytochemical assay; high PR content was observed in cisternae, transitional, meningothelial, and low-grade meningiomas. Only 11 meningiomas showed more than 1% Ki67 immunoreactive nuclei. These meningiomas were usually located in the convexity and were of high histological grade. Estrogen-regulated protein immunoreactivity was observed in 34 meningiomas but the number of immunoreactive nuclei was low. The pS2 immunocytochemical assay was not related to clinicopathological features but was preferentially observed in PR-negative meningiomas. The results of this study are compared with those previously reported, and the function and regulation of PR's in meningiomas is discussed. The results indicate that 1) regulation of PR's and pS2 proteins in meningiomas differs from regulation in estrogen-dependent tissues such as breast or endometrium; 2) interruption of hormonal therapy in women presenting with a meningioma is not absolutely necessary; 3) meningiomas have different biological properties according to their clinicopathological features; and 4) future studies of hormonal clinical trials should be performed on well-defined meningioma subgroups.

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