Meningiomas, dicentric chromosomes, gliomas, and telomerase activity.

PubMed

Carroll, T; Maltby, E; Brock, I; Royds, J; Timperley, W; Jellinek, D

1999-08-01

Lack of telomere maintenance during cell replication leads to telomere erosion and loss of function. This can result in telomere associations which probably cause the dicentric chromosomes seen in some tumour cells. One mechanism of telomere maintenance in dividing cells is the action of telomerase, a ribonucleoprotein enzyme that adds TTAGGG repeats onto telomeres and compensates for their shortening during cell division. Over 90 per cent of extracranial malignant neoplasms have been found to have telomerase activity. This study sought to determine if there was a relationship between absence of telomerase activity and presence of dicentric chromosomes in meningiomas and to what extent the other main group of central nervous system tumours, the gliomas, expressed telomerase activity. Telomerase activity was measured on 25 meningiomas and 29 gliomas. Four of the meningiomas were atypical variants and 11 were positive for dicentric chromosomes. Twenty-five of 29 gliomas were glioblastoma multiforme tumours. Measures were taken to ensure absence of false positives due to primer-dimer interaction and false negatives due to protein degradation or the presence of Taq polymerase inhibitors. All 25 meningiomas and the four low-grade gliomas (WHO grade II) were telomerase activity-negative. Seven (28 per cent) of the 25 glioblastoma multiforme tumours showed telomerase activity. The absence of telomerase activity in meningiomas and the high frequency of telomere associations support the hypothesis that these tumours are benign, transformed but pre-crisis. The relatively low frequency of telomerase activity in the malignant glioblastoma multiforme suggests that most of these tumours may have other mechanisms of telomere maintenance and that the potentially therapeutic telomerase inhibitors will not be of great value in the future management of the majority of patients suffering from these tumours. Copyright 1999 John Wiley & Sons, Ltd.

Histopathology and prognosis in human meningiomas.

PubMed

Backer-Grøndahl, Thomas; Moen, Bjørnar H; Sundstrøm, Stein H; Torp, Sverre H

2014-09-01

Histopathological grading of human meningiomas is based on criteria adopted by the World Health Organization (WHO). However, interpretation of the defined histopathological criteria is often subjective. The aim of this study was to investigate the clinical and histopathological features in these tumours associated with patient survival. This enables evaluation of current grading guidelines and practice. In this study, 196 primary, intracranial, and consecutively treated patients from one institution were included. All histological sections were reviewed. Survival data were controlled with the Norwegian Cause of Death Registry. Falcine location, sheet-like growth, frequent mitoses, subtotal resection grade, and absence of psammoma bodies were strong prognostic factors. Of these factors, the latter two were statistically significantly associated with decreased time to recurrence in multivariate analyses. The WHO 2000 and 2007 classifications were associated with decreased time to recurrence. However, the grading criteria suggested by Ho et al. (2002) and in this study achieved stronger prognostic values. Easily recognizable histopathological criteria are essential in tumour grading. We suggest that any two of the following three variables can be used to recognize atypical (grade II) meningiomas: absence of psammoma bodies, presence of necrosis, and/or ≥4 mitoses per 10 high power fields. © 2014 APMIS. Published by John Wiley & Sons Ltd.

RO4929097, Temozolomide, and Radiation Therapy in Treating Patients With Newly Diagnosed Malignant Glioma

ClinicalTrials.gov

2015-09-28

Acoustic Schwannoma; Adult Anaplastic (Malignant) Meningioma; Adult Anaplastic Astrocytoma; Adult Anaplastic Ependymoma; Adult Brain Stem Glioma; Adult Choroid Plexus Neoplasm; Adult Craniopharyngioma; Adult Diffuse Astrocytoma; Adult Ependymoblastoma; Adult Ependymoma; Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Adult Grade I Meningioma; Adult Grade II Meningioma; Adult Medulloblastoma; Adult Mixed Glioma; Adult Myxopapillary Ependymoma; Adult Oligodendroglioma; Adult Papillary Meningioma; Adult Pilocytic Astrocytoma; Adult Pineal Gland Astrocytoma; Adult Pineoblastoma; Adult Pineocytoma; Adult Primary Melanocytic Lesion of Meninges; Adult Subependymal Giant Cell Astrocytoma; Adult Subependymoma; Adult Supratentorial Primitive Neuroectodermal Tumor; Malignant Adult Intracranial Hemangiopericytoma

Intracranial meningioma as primary presentation for an undiagnosed collision metastatic breast cancer: Case report and literature review

PubMed Central

Farrag, Ashraf; Ansari, Jawaher; Ali, Muhammad; Sunbuli, Ghanem; Kassem, Hassan; Al Hamad, Abdul-Aziz

2018-01-01

Intracranial metastasis from breast cancer is a relatively common finding, however, the appearance of breast cancer metastasis in a meningioma is very rare. Several cases of tumor-to-tumor metastasis and collision tumors have been reported previously, with meningioma being implicated as the most common benign intracranial neoplasm to harbour the metastasis. Occasionally, the discovery of a tumor-to-meningioma metastasis may herald the diagnosis of an occult primary malignancy. Careful histopathological assessment of the resected meningioma specimen is pivotal to the management of these patients, as this will alter the treatment plan and prognosis considerably. Intracranial meningioma with collision breast cancer as primary presentation of an undiagnosed metastatic breast cancer is extremely rare. The current study presents a case of intracranial meningioma with collision breast cancer as a primary presentation, and reviews the available evidence for this unusual disease entity. PMID:29725531

Intracranial meningioma as primary presentation for an undiagnosed collision metastatic breast cancer: Case report and literature review.

PubMed

Farrag, Ashraf; Ansari, Jawaher; Ali, Muhammad; Sunbuli, Ghanem; Kassem, Hassan; Al Hamad, Abdul-Aziz

2018-05-01

Intracranial metastasis from breast cancer is a relatively common finding, however, the appearance of breast cancer metastasis in a meningioma is very rare. Several cases of tumor-to-tumor metastasis and collision tumors have been reported previously, with meningioma being implicated as the most common benign intracranial neoplasm to harbour the metastasis. Occasionally, the discovery of a tumor-to-meningioma metastasis may herald the diagnosis of an occult primary malignancy. Careful histopathological assessment of the resected meningioma specimen is pivotal to the management of these patients, as this will alter the treatment plan and prognosis considerably. Intracranial meningioma with collision breast cancer as primary presentation of an undiagnosed metastatic breast cancer is extremely rare. The current study presents a case of intracranial meningioma with collision breast cancer as a primary presentation, and reviews the available evidence for this unusual disease entity.

Tenascin in meningioma: expression is correlated with anaplasia, vascular endothelial growth factor expression, and peritumoral edema but not with tumor border shape.

PubMed

Kiliç, Türker; Bayri, Yaşar; Ozduman, Koray; Acar, Melih; Diren, Semin; Kurtkaya, Ozlem; Ekinci, Gazanfer; Buğra, Kuyaş; Sav, Aydin; Ozek, M Memet; Pamir, M Necmettin

2002-07-01

Tenascin is an extracellular matrix glycoprotein that is expressed during embryogenesis, inflammation, angiogenesis, and carcinogenesis. The aim of this study was to investigate how tenascin expression relates to histological grade, angiogenesis, and radiological findings in meningiomas. Twenty typical, 20 atypical, and 5 malignant meningiomas were studied retrospectively. Tenascin expression and vascular endothelial growth factor (VEGF) expression in the tumor tissue were investigated by immunohistochemistry. Tenascin messenger ribonucleic acid expression was also studied by comparative reverse transcriptase-polymerase chain reaction. Magnetic resonance images from each case were assessed for peritumoral edema and tumor border shape. The atypical and malignant meningiomas showed higher levels of tenascin expression than the typical meningiomas. The more sensitive messenger ribonucleic acid-based methods confirmed this finding. Tenascin expression was correlated with peritumoral edema and VEGF expression but not with tumor border shape. In the 13 tumors with marked tenascin expression, peritumoral edema was Grade 0 in one, Grade 1 in three, and Grade 2 in nine specimens. In the same 13 tumors, VEGF expression was Grade 1 in five and Grade 2 in eight specimens, and the findings for tumor border shape were Grade 0 in seven, Grade 1 in four, and Grade 2 in two specimens. In meningiomas, tenascin expression is correlated with anaplasia, tumor-associated edema, and VEGF expression but not with tumor border shape. This protein may play a role in the neoplastic and/or angiogenic processes in atypical and malignant meningiomas and may thus be a potential target for meningioma therapy.

CXCR4 and SDF1 expression in human meningiomas: a proliferative role in tumoral meningothelial cells in vitro.

PubMed

Bajetto, Adriana; Barbieri, Federica; Pattarozzi, Alessandra; Dorcaratto, Alessandra; Porcile, Carola; Ravetti, Jean Louis; Zona, Gianluigi; Spaziante, Renato; Schettini, Gennaro; Florio, Tullio

2007-01-01

Chemokines participate in cellular processes associated with tumor proliferation, migration, and angiogenesis. We previously demonstrated that stromal cell-derived factor 1 (SDF1) exerts a mitogenic activity in glioblastomas through the activation of its receptor CXCR4. Here we studied the expression of this chemokine in human meningiomas and its possible role in cell proliferation. Reverse transcriptase-PCR analysis for CXCR4 and SDF1 was performed on 55 human meningiomas (47 WHO grade I, 5 WHO II, and 3 WHO III). Immunolabeling for CXCR4 and SDF1 was performed on paraffin-embedded sections of these tumors. [(3)H]Thymidine uptake and Western blot analyses were performed on primary meningeal cell cultures of tumors to evaluate the proliferative activity of human SDF1alpha (hSDF1alpha) in vitro and the involvement of extracellular signal-regulated kinase 1/2 (ERK1/2) activation in this process. CXCR4 mRNA was expressed by 78% of the tumor specimens and SDF1 mRNA by 53%. CXCR4 and SDF1 were often detected in the same tumor tissues and colocalized with epithelial membrane antigen immunostaining. In 9 of 12 primary cultures from meningiomas, hSDF1alpha induced significant cell proliferation that was strongly reduced by the mitogen-activated protein kinase kinase inhibitor PD98059, involving ERK1/2 activation in the proliferative signal of hSDF1alpha. In fact, CXCR4 stimulation led to ERK1/2 phosphorylation/activation. In addition, the hSDF1alpha-induced cell proliferation was significantly correlated with the MIB1 staining index in the corresponding surgical specimen. In conclusion, we found that human meningiomas express CXCR4 and SDF1 and that hSDF1alpha induces proliferation in primary meningioma cell cultures through the activation of ERK1/2.

[Multiple meningiomas].

PubMed

Terrier, L-M; François, P

2016-06-01

Multiple meningiomas (MMs) or meningiomatosis are defined by the presence of at least 2 lesions that appear simultaneously or not, at different intracranial locations, without the association of neurofibromatosis. They present 1-9 % of meningiomas with a female predominance. The occurrence of multiple meningiomas is not clear. There are 2 main hypotheses for their development, one that supports the independent evolution of these tumors and the other, completely opposite, that suggests the propagation of tumor cells of a unique clone transformation, through cerebrospinal fluid. NF2 gene mutation is an important intrinsic risk factor in the etiology of multiple meningiomas and some exogenous risk factors have been suspected but only ionizing radiation exposure has been proven. These tumors can grow anywhere in the skull but they are more frequently observed in supratentorial locations. Their histologic types are similar to unique meningiomas of psammomatous, fibroblastic, meningothelial or transitional type and in most cases are benign tumors. The prognosis of these tumors is eventually good and does not differ from the unique tumors except for the cases of radiation-induced multiple meningiomas, in the context of NF2 or when diagnosed in children where the outcome is less favorable. Each meningioma lesion should be dealt with individually and their multiple character should not justify their resection at all costs. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Secondary malignancy following radiotherapy for thyroid eye disease.

PubMed

Gillis, Christopher C; Chang, Eun Hae; Al-Kharazi, Khalid; Pickles, Tom

2016-01-01

To describe the first case of a secondary meningioma in a patient after radiation treatment for thyroid eye disease (TED). Secondarily to identify any additional cases of secondary malignancy resulting from radiotherapy for thyroid eye disease from our institutional experience. Thyroid eye disease (TED) is a self-limiting auto-immune disorder causing expansion of orbital soft tissue from deposition of glycosaminoglycans and collagen, leading to significant cosmetic and functional morbidity. Established management options for TED include: glucocorticosteroids, orbital radiotherapy, and surgical orbital decompression. Two large series on radiotherapy for TED have been reported without any cases of secondary malignancy. The case of a patient with visual failure, found to have a sphenoid wing meningioma after previous TED radiotherapy is described. We then reviewed 575 patients with at least 3-year follow-up receiving radiotherapy for TED at British Columbia Cancer Agency to identify other possible secondary malignancies. The patient had postoperative improvement in her vision without any identified complications. Three additional cases of hematologic malignancy were identified. The calculated risk in our population of developing a radiation-induced meningioma after TED with at least 3 years of follow-up of is 0.17% (1/575); with hematopoetic malignancies the risk for secondary malignancy is 0.7% (4/575). Our calculated risk for secondary malignancy (0.17%, 0.7%) is similar to the reported theoretical risk published in the literature (0.3-1.2%). There is real risk for the development of a secondary malignancy after radiotherapy treatment of TED and treatment options should include consideration for this potential.

Effects of sex on the incidence and prognosis of spinal meningiomas: a Surveillance, Epidemiology, and End Results study.

PubMed

Westwick, Harrison J; Shamji, Mohammed F

2015-09-01

Most spinal meningiomas are intradural lesions in the thoracic spine that present with both local pain and myelopathy. By using the large prospective Surveillance, Epidemiology, and End Results (SEER) database, the authors studied the incidence of spinal meningiomas and examined demographic and treatment factors predictive of death. Using SEER*Stat software, the authors queried the SEER database for cases of spinal meningioma between 2000 and 2010. From the results, tumor incidence and demographic statistics were computed; incidence was analyzed as a function of tumor location, pathology, age, sex, and malignancy code. Survival was analyzed by using a Cox proportional hazards ratio in SPSS for age, sex, marital status, primary site, size quartile, treatment modality, and malignancy code. In this analysis, significance was set at a p value of 0.05. The 1709 spinal meningiomas reported in the SEER database represented 30.7% of all primary intradural spinal tumors and 7.9% of all meningiomas. These meningiomas occurred at an age-adjusted incidence of 0.193 (95% CI 0.183-0.202) per 100,000 population and were closely related to sex (337 [19.7%] male patients and 1372 [80.3%] female patients). The Cox hazard function for mortality in males was higher (2.4 [95% CI1.7-3.5]) and statistically significant, despite the lower lesion incidence in males. All-cause survival was lowest in patients older than 80 years. Primary site and treatment modality were not significant predictors of mortality. Spinal meningiomas represent a significant fraction of all primary intradural spinal tumors and of all meningiomas. The results of this study establish the association of lesion incidence and survival with sex, with a less frequent incidence in but greater mortality among males.

Immunohistochemical profile of neurotrophins in human cranial dura mater and meningiomas.

PubMed

Artico, Marco; Bronzetti, Elena; Pompili, Elena; Ionta, Brunella; Alicino, Valentina; D'Ambrosio, Anna; Santoro, Antonio; Pastore, Francesco S; Elenkov, Ilia; Fumagalli, Lorenzo

2009-06-01

The immunohistochemical profile of neurotrophins and their receptors in the human cranial dura mater was studied by examining certain dural zones in specimens harvested from different regions (frontal, temporal, parietal and occipital). Dural specimens were obtained during neurosurgical operations performed in ten patients for surgical treatment of intracranial lesions (meningiomas, traumas, gliomas, vascular malformations). The dural fragments were taken from the area of the craniotomy at least 8 cm from the lesion as well as from the area in which the meningioma had its dural attachment. Immunohistochemical characterization and distribution of neurotrophins, with their receptors, were analyzed. The concrete role played by these neurotrophic factors in general regulation, vascular permeability, algic responsivity and release of locally active substances in the human dura mater is still controversial. Our study revealed a general structural alteration of dural tissue due to the invasivity of meningiomatous lesions, together with an improved expression of brain derived neurotrophic factor (BDNF) in highly proliferating neoplastic cells and an evident production of nerve growth factor (NGF) in inflammatory cells, suggesting that BDNF has a role in supporting the proliferation rate of neoplastic cells, while NGF is involved in the activation of a chronic inflammatory response in neoplastic areas.

Radiation-induced meningiomas: Experience at the Mount Sinai Hospital and review of the literature

DOE Office of Scientific and Technical Information (OSTI.GOV)

Harrison, M.J.; Wolfe, D.E.; Lau, T.S.

1991-10-01

From the records of The Mount Sinai Hospital, seven cases which met established criteria for radiation-induced meningiomas were identified. This represents the largest series of radiogenic meningiomas documented in North America and includes both intracranial and intraspinal tumors. The records and pathological specimens were reviewed and these data analyzed with other cases retrieved from the world literature. This study reveals that radiation-induced meningiomas can be categorized into three groups based on the amount of radiation administered: (1) low dose; (2) moderate dose and miscellaneous; and (3) high dose. The overwhelming majority of cases had received low-dose irradiation (800 rad) tomore » the scalp for tinea capitis and the second largest group resulted from high-dose irradiation for primary brain tumors (greater than 2000 rad). The unique features distinguishing radiation-induced meningiomas from other meningiomas are reviewed. Although histologically atypical tumors were common in this series, overt malignancy was not encountered. The preoperative management of these lesions should include angiography to evaluate for large-vessel occlusive vasculopathy, a known association of meningiomas induced by high-dose irradiation. Given the propensity these tumors possess for recurrence, a wide bony and dural margin is recommended at surgical resection. 102 references.« less

Expression of CXCR7 chemokine receptor in human meningioma cells and in intratumoral microvasculature.

PubMed

Würth, Roberto; Barbieri, Federica; Bajetto, Adriana; Pattarozzi, Alessandra; Gatti, Monica; Porcile, Carola; Zona, Gianluigi; Ravetti, Jean-Louis; Spaziante, Renato; Florio, Tullio

2011-05-01

CXCR4 and CXCR7 chemokine receptors, and their ligands CXCL11 and CXCL12, have been often involved in tumor cell proliferation and survival. We report the expression pattern of these ligand/receptor pairs in 22 human meningiomas. High CXCR7 and CXCL12 expression was associated with high-proliferative tumors. CXCR7 levels were correlated to the content of both ligands, suggesting a possible autocrine regulation. CXCR4 and CXCL12 were homogeneously expressed within tumor cells, while CXCR7 was mainly detected in tumor endothelial cells and CXCL11 in pericytes. Our results highlight the preferential CXCR7 and CXCL12 expression within more aggressive tumors and the possible role of CXCR7 in meningioma vascularization. Copyright © 2011 Elsevier B.V. All rights reserved.

Favorable Outcomes of Pediatric Patients Treated With Radiotherapy to the Central Nervous System Who Develop Radiation-Induced Meningiomas

DOE Office of Scientific and Technical Information (OSTI.GOV)

Galloway, Thomas J.; Indelicato, Daniel J., E-mail: dindelicato@floridaproton.or; University of Florida Proton Therapy Institute, Jacksonville, FL

Purpose: To report the outcome of patients treated at the University of Florida who developed meningiomas after radiation to the central nervous system (CNS) for childhood cancer. Methods and Materials: We retrospectively identified 10 patients aged {<=}19 years who received radiotherapy to sites in the craniospinal axis and subsequently developed a meningioma. We report the histology of the radiation-induced meningioma, treatment received, and ultimate outcome among this cohort of patients. Results: Meningioma was diagnosed at a median of 23.5 years after completion of the primary radiation. Fifty percent of second meningiomas were World Health Organization Grade 2 (atypical) or higher.more » All cases were managed with a single modality: resection alone (n = 7), fractionated radiotherapy (n = 2), and stereotactic radiosurgery (n = 1). The actuarial event-free survival and overall survival rate at 5 years after treatment for a radiation-induced meningioma was 89%. Three patients who underwent resection for retreatment experienced a Grade 3 toxicity. Conclusions: Radiation-induced meningiomas after treatment of pediatric CNS tumors are effectively managed with single-modality therapy. Such late-effect data inform the overall therapeutic ratio and support the continued role of selective irradiation in managing pediatric CNS malignancies.« less

Bevacizumab therapy for adults with recurrent/progressive meningioma: a retrospective series

PubMed Central

Lou, Emil; Sumrall, Ashley L.; Turner, Scott; Peters, Katherine B.; Desjardins, Annick; Vredenburgh, James J.; McLendon, Roger E.; Herndon, James E.; McSherry, Frances; Norfleet, Julie; Friedman, Henry S.

2012-01-01

Intracranial meningiomas are often indolent tumors which typically grow over years to decades. Nonetheless, meningiomas that progress after maximum safe resection and radiation therapy pose a significant therapeutic challenge and effective therapies have yet to be identified. Preclinical studies implicate angiogenesis in the pathophysiology of more aggressive meningiomas, suggesting that anti-angiogenic therapies may be of utility in this setting. We performed a retrospective review of fourteen patients with recurrent meningioma treated at Duke University Medical Center with bevacizumab, a humanized monoclonal antibody against vascular endothelial growth factor, administered either alone or in combination with chemotherapy. Most patients were heavily pre-treated. Progression-free survival at 6 months was 86 % and was comparable regardless of meningioma grade and whether bevacizumab was administered as monotherapy or in combination with chemotherapy. Most toxicities were mild however single patients developed CNS hemorrhage (grade 1) and intestinal perforation (grade 4), respectively. Bevacizumab can be administered safely to patients with meningioma and appears to be associated with encouraging anti-tumor effect when administered as either a single agent or in combination with chemotherapy. Phase II trials investigating bevacizumab in patients with progressive/recurrent meningioma are warranted. PMID:22535433

Epidemiology and etiology of meningioma

PubMed Central

Wrensch, Margaret; Claus, Elizabeth B.

2010-01-01

Although most meningiomas are encapsulated and benign tumors with limited numbers of genetic aberrations, their intracranial location often leads to serious and potentially lethal consequences. They are the most frequently diagnosed primary brain tumor accounting for 33.8% of all primary brain and central nervous system tumors reported in the United States between 2002 and 2006. Inherited susceptibility to meningioma is suggested both by family history and candidate gene studies in DNA repair genes. People with certain mutations in the neurofibromatosis gene (NF2) have a very substantial increased risk for meningioma. High dose ionizing radiation exposure is an established risk factor for meningioma, and lower doses may also increase risk, but which types and doses are controversial or understudied. Because women are twice as likely as men to develop meningiomas and these tumors harbor hormone receptors, an etiologic role for hormones (both endogenous and exogenous) has been hypothesized. The extent to which immunologic factors influence meningioma etiology has been largely unexplored. Growing emphasis on brain tumor research coupled with the advent of new genetic and molecular epidemiologic tools in genetic and molecular epidemiology promise hope for advancing knowledge about the causes of intra-cranial meningioma. In this review, we highlight current knowledge about meningioma epidemiology and etiology and suggest future research directions. PMID:20821343

RNA-seq transcriptome analysis of formalin fixed, paraffin-embedded canine meningioma

PubMed Central

Grenier, Jennifer K.; Foureman, Polly A.; Sloma, Erica A.

2017-01-01

Meningiomas are the most commonly reported primary intracranial tumor in dogs and humans and between the two species there are similarities in histology and biologic behavior. Due to these similarities, dogs have been proposed as models for meningioma pathobiology. However, little is known about specific pathways and individual genes that are involved in the development and progression of canine meningioma. In addition, studies are lacking that utilize RNAseq to characterize gene expression in clinical cases of canine meningioma. The primary objective of this study was to develop a technique for which high quality RNA can be extracted from formalin-fixed, paraffin embedded tissue and then used for transcriptome analysis to determine patterns of gene expression. RNA was extracted from thirteen canine meningiomas–eleven from formalin fixed and two flash-frozen. These represented six grade I and seven grade II meningiomas based on the World Health Organization classification system for human meningioma. RNA was also extracted from fresh frozen leptomeninges from three control dogs for comparison. RNAseq libraries made from formalin fixed tissue were of sufficient quality to successfully identify 125 significantly differentially expressed genes, the majority of which were related to oncogenic processes. Twelve genes (AQP1, BMPER, FBLN2, FRZB, MEDAG, MYC, PAMR1, PDGFRL, PDPN, PECAM1, PERP, ZC2HC1C) were validated using qPCR. Among the differentially expressed genes were oncogenes, tumor suppressors, transcription factors, VEGF-related genes, and members of the WNT pathway. Our work demonstrates that RNA of sufficient quality can be extracted from FFPE canine meningioma samples to provide biologically relevant transcriptome analyses using a next-generation sequencing technique, such as RNA-seq. PMID:29073243

Cystic meningiomas.

PubMed

Borovich, B; Guilburd, J N; Doron, Y; Soustiel, J F; Zaaroor, M; Braun, J; Gruszkiewicz, J; Feinsod, M

1988-01-01

Four cases of cystic meningiomas were found among 194 meningiomas diagnosed by computed tomography (CT) and operated on during a 7 year period, an incidence of 2%. The cysts were in all cases peritumoral. The cyst's wall was the brain itself, and the ependymal ventricular wall was part of their medial boundary. They contained xanthochromic fluid with a high protein content. Three meningiomas were parasagittal and one was adjacent to the pteryon and the external part of the sphenoid ridge. The mural nodules were in 2 cases apparent single nodes although in one it was part of multiple distant and regional growths, in another the tumour was built by the aggregation of 2 nodes, the remaining case was an "en plaque" meningioma. All were definitely attached to the dura. Histological pattern was different in every case. Those parasagittal were: one pure meningotheliomatous, one mixed meningotheliomatous with pseudo psammomatous and lipoblastic sections and one highly vascular angioblastic; the pteryonal case was psammomatous and microcystic. CT diagnosis is difficult because glial, metastatic and other tumours may look cystic and resemble cystic meningiomas. Nevertheless in 3 cases the correct diagnosis was suspected preoperatively because the solid portion of the tumour showed intense and homogeneous contrast enhancement with a sharp edge and was located adjacent to the dura. On the other hand in the remaining case, the parasagittal solid tumour was not readily apparent on CT (the "en plaque", case), and the tentative preoperative diagnosis was of an epidermoid tumour.(ABSTRACT TRUNCATED AT 250 WORDS)

Expression of nestin, mesothelin and epithelial membrane antigen (EMA) in developing and adult human meninges and meningiomas.

PubMed

Petricevic, Josko; Forempoher, Gea; Ostojic, Ljerka; Mardesic-Brakus, Snjezana; Andjelinovic, Simun; Vukojevic, Katarina; Saraga-Babic, Mirna

2011-11-01

The spatial and temporal pattern of appearance of nestin, epithelial membrane antigen (EMA) and mesothelin proteins was immunohistochemically determined in the cells of normal developing and adult human meninges and meningiomas. Human meninges developed as two mesenchymal condensations in the head region. The simple squamous epithelium on the surface of leptomeninges developed during mesenchymal to epithelial transformation. Nestin appeared for the first time in week 7, EMA in week 8, while mesothelin appeared in week 22 of development. In the late fetal period and after birth, nestin expression decreased, whereas expression of EMA and mesothelin increased. EMA appeared in all surface epithelial cells and nodules, while mesothelin was found only in some of them. In adult meninges, all three proteins were predominantly localized in the surface epithelium and meningeal nodules. In meningothelial meningiomas (WHO grade I), EMA was detected in all tumor cells except in the endothelial cells, mesothelin characterized nests of tumor cells, while nestin was found predominantly in the walls of blood vessels. The distribution pattern of those proteins in normal meningeal and tumor cells indicates that nestin might characterize immature cells, while EMA and mesothelin appeared in maturing epithelial cells. Neoplastic transformation of these specific cell lineages contributes to the cell population in meningiomas. Copyright © 2010 Elsevier GmbH. All rights reserved.

EG-09EPIGENETIC PROFILING REVEALS A CpG HYPERMETHYLATION PHENOTYPE (CIMP) ASSOCIATED WITH WORSE PROGRESSION-FREE SURVIVAL IN MENINGIOMA

PubMed Central

Olar, Adriana; Wani, Khalida; Mansouri, Alireza; Zadeh, Gelareh; Wilson, Charmaine; DeMonte, Franco; Fuller, Gregory; Jones, David; Pfister, Stefan; von Deimling, Andreas; Sulman, Erik; Aldape, Kenneth

2014-01-01

BACKGROUND: Methylation profiling of solid tumors has revealed biologic subtypes, often with clinical implications. Methylation profiles of meningioma and their clinical implications are not well understood. METHODS: Ninety-two meningioma samples (n = 44 test set and n = 48 validation set) were profiled using the Illumina HumanMethylation450 BeadChip. Unsupervised clustering and analyses for recurrence-free survival (RFS) were performed. RESULTS: Unsupervised clustering of the test set using approximately 900 highly variable markers identified two clearly defined methylation subgroups. One of the groups (n = 19) showed global hypermethylation of a set of markers, analogous to CpG island methylator phenotype (CIMP). These findings were reproducible in the validation set, with 18/48 samples showing the CIMP-positive phenotype. Importantly, of 347 highly variable markers common to both the test and validation set analyses, 107 defined CIMP in the test set and 94 defined CIMP in the validation set, with an overlap of 83 markers between the two datasets. This number is much greater than expected by chance indicating reproducibly of the hypermethylated markers that define CIMP in meningioma. With respect to clinical correlation, the 37 CIMP-positive cases displayed significantly shorter RFS compared to the 55 non-CIMP cases (hazard ratio 2.9, p = 0.013). In an effort to develop a preliminary outcome predictor, a 155-marker subset correlated with RFS was identified in the test dataset. When interrogated in the validation dataset, this 155-marker subset showed a statistical trend (p < 0.1) towards distinguishing survival groups. CONCLUSIONS: This study defines the existence of a CIMP phenotype in meningioma, which involves a substantial proportion (37/92, 40%) of samples with clinical implications. Ongoing work will expand this cohort and examine identification of additional biologic differences (mutational and DNA copy number analysis) to further characterize the aberrant

Angioblastic meningioma with hepatic metastasis

PubMed Central

Petito, Carol K.; Porro, Robert S.

1971-01-01

Infrequently, intracranial neoplasms metastasize to extracranial sites. In 1963, Glasauer and Yuan reviewed the 88 reported cases of metastatic intracranial tumours of which approximately two-fifths were meningiomas. This report concerns an angioblastic meningioma with a large hepatic metastasis. Cushing's original classification of angioblastic meningiomas and the differential diagnosis between these tumours and the haemangiopericytoma and cerebellar haemangioblastoma are discussed. Images PMID:5166210

Phase II study of monthly pasireotide LAR (SOM230C) for recurrent or progressive meningioma

PubMed Central

Norden, Andrew D.; Ligon, Keith L.; Hammond, Samantha N.; Muzikansky, Alona; Reardon, David A.; Kaley, Thomas J.; Batchelor, Tracy T.; Plotkin, Scott R.; Raizer, Jeffrey J.; Wong, Eric T.; Drappatz, Jan; Lesser, Glenn J.; Haidar, Sam; Beroukhim, Rameen; Lee, Eudocia Q.; Doherty, Lisa; Lafrankie, Debra; Gaffey, Sarah C.; Gerard, Mary; Smith, Katrina H.; McCluskey, Christine; Phuphanich, Surasak

2015-01-01

Objective: A subset of meningiomas recur after surgery and radiation therapy, but no medical therapy for recurrent meningioma has proven effective. Methods: Pasireotide LAR is a long-acting somatostatin analog that may inhibit meningioma growth. This was a phase II trial in patients with histologically confirmed recurrent or progressive meningioma designed to evaluate whether pasireotide LAR prolongs progression-free survival at 6 months (PFS6). Patients were stratified by histology (atypical [World Health Organization grade 2] and malignant [grade 3] meningiomas in cohort A and benign [grade 3] in cohort B). Results: Eighteen patients were accrued in cohort A and 16 in cohort B. Cohort A had median age 59 years, median Karnofsky performance status 80, 17 (94%) had previous radiation therapy, and 11 (61%) showed high octreotide uptake. Cohort B had median age 52 years, median Karnofsky performance status 90, 11 (69%) had previous radiation therapy, and 12 (75%) showed high octreotide uptake. There were no radiographic responses to pasireotide LAR therapy in either cohort. Twelve patients (67%) in cohort A and 13 (81%) in cohort B achieved stable disease. In cohort A, PFS6 was 17% and median PFS 15 weeks (95% confidence interval: 8–20). In cohort B, PFS6 was 50% and median PFS 26 weeks (12–43). Treatment was well tolerated. Octreotide uptake and insulin-like growth factor–1 levels did not predict outcome. Expression of somatostatin receptor 3 predicted favorable PFS and overall survival. Conclusions: Pasireotide LAR has limited activity in recurrent meningiomas. The finding that somatostatin receptor 3 is associated with favorable outcomes warrants further investigation. Classification of evidence: This study provides Class IV evidence that in patients with recurrent or progressive meningioma, pasireotide LAR does not significantly increase the proportion of patients with PFS at 6 months. PMID:25527270

Calvarial ectopic meningothelial meningioma

PubMed Central

Vital, Roberto Bezerra; Hamamoto Filho, Pedro Tadao; Lapate, Renan Luiz; Martins, Vinícius Zanin; de Oliveira Lima, Flávio; Romero, Flávio Ramalho; Zanini, Marco Antônio

2015-01-01

Background Meningiomas are the most common benign neoplasm of the brain whereas ectopic presentation, although reported, is rare. Among these ectopic tumors, there are a group of purely intraosseous meningiomas, which usually are diagnosed differentially from common primary osseous tumor such as fibrous dysplasia and osteoid osteoma. Case description We report a 62-year-old female with a history of headaches and 6 months of progressive right parietal bulging, with no neurological signs. Parietal craniotomy was performed with immediate titanium cranioplasty of the parietal convexity. Histopathology exams revealed an ectopic intradiploic meningioma without invasion of cortical layers, with positive staining for progesterone receptors and epithelial membrane antigen. Conclusions Ectopic intraosseous meningiomas remain a rare neoplasm with only a few cases reported. The main theories to justify the unusual topography appear to be embryological remains of neuroectodermal tissue or cellular dedifferentiation. Surgical treatment seems the best curative option. PMID:25805612

Impact of 1p/19q codeletion on the diagnosis and prognosis of different grades of meningioma.

PubMed

Basaran, Recep; Uslu, Serap; Gucluer, Berrin; Onoz, Mustafa; Isik, Nejat; Tiryaki, Mehmet; Yakicier, Cengiz; Sav, Aydin; Elmaci, Ilhan

2016-10-01

Meningiomas are one of the most common tumours to affect the central nervous system. Genetic mutations are important in meningeal tumourigenesis, progression and prognosis. In this study, we aimed to examine the effect of 1p/19q deletion on the diagnosis and prognosis of meningioma subtypes using the fluorescence in situ hybridization (FISH) method. Twenty-four patients with meningioma were retrospectively studied. Tumour samples were obtained from 10 typical, 11 atypical and three anaplastic malignant meningiomas. The most representative tumour sections were screened for 1p/19q deletion using the FISH method. Of the 24 patients, eight were women (33.3%) and 16 (66.7%) were men. The mean age was 56.6 years. The higher-grade meningioma was usually seen in males and had a higher rate of deletion on 1p (p = 0.001). There was a statistically significant difference between the grades and the rate of deletion on 19q (p = 0.042) and between the grades and the rates of polysomy, monosomy and amplification on 19q (p = 0.002; p = 0.001; p = 0.002, respectively). There was no statistical difference between 1p/19q codeletion and the grades of meningioma (p > 0.05). We detected higher level of Ki-67 in the condition of codeletion but did not find a statistical difference (p = 0.0553). Deletion on 1p, as well as deletion, polysomy, monosomy and amplification on 19q, are detected more frequently in high grade meningiomas. This amplification is most likely due to the amplification of oncogenes.

Quantitative and qualitative 5-aminolevulinic acid–induced protoporphyrin IX fluorescence in skull base meningiomas

PubMed Central

Bekelis, Kimon; Valdés, Pablo A.; Erkmen, Kadir; Leblond, Frederic; Kim, Anthony; Wilson, Brian C.; Harris, Brent T.; Paulsen, Keith D.; Roberts, David W.

2011-01-01

Object Complete resection of skull base meningiomas provides patients with the best chance for a cure; however, surgery is frequently difficult given the proximity of lesions to vital structures, such as cranial nerves, major vessels, and venous sinuses. Accurate discrimination between tumor and normal tissue is crucial for optimal tumor resection. Qualitative assessment of protoporphyrin IX (PpIX) fluorescence following the exogenous administration of 5-aminolevulinic acid (ALA) has demonstrated utility in malignant glioma resection but limited use in meningiomas. Here the authors demonstrate the use of ALA-induced PpIX fluorescence guidance in resecting a skull base meningioma and elaborate on the advantages and disadvantages provided by both quantitative and qualitative fluorescence methodologies in skull base meningioma resection. Methods A 52-year-old patient with a sphenoid wing WHO Grade I meningioma underwent tumor resection as part of an institutional review board–approved prospective study of fluorescence-guided resection. A surgical microscope modified for fluorescence imaging was used for the qualitative assessment of visible fluorescence, and an intraoperative probe for in situ fluorescence detection was utilized for quantitative measurements of PpIX. The authors assessed the detection capabilities of both the qualitative and quantitative fluorescence approaches. Results The patient harboring a sphenoid wing meningioma with intraorbital extension underwent radical resection of the tumor with both visibly and nonvisibly fluorescent regions. The patient underwent a complete resection without any complications. Some areas of the tumor demonstrated visible fluorescence. The quantitative probe detected neoplastic tissue better than the qualitative modified surgical microscope. The intraoperative probe was particularly useful in areas that did not reveal visible fluorescence, and tissue from these areas was confirmed as tumor following histopathological

Confocal Microscopy for the Histological Fluorescence Pattern of a Recurrent Atypical Meningioma: Case Report

PubMed Central

Whitson, Wesley J.; Valdes, Pablo A.; Harris, Brent T.; Paulsen, Keith D.; Roberts, David W.

2013-01-01

Background and Importance Fluorescence-guided resection with 5-aminolevulinic acid (5-ALA), which has shown promising results in the resection of malignant gliomas, has been used for meningioma resection in an attempt to more clearly delineate the tumor margin. However, no article has investigated the fluorescence pattern of meningiomas on a histological level. Understanding the microscopic pattern of fluorescence could help assess the precision and utility of using 5-ALA for these tumors. We present the case of a recurrent atypical meningioma operated on with 5-ALA fluorescence-guided resection for delineation of tumor tissue from surrounding uninvolved dura. Clinical Presentation A 53-year-old woman presented with recurrent atypical meningioma of the falx. Prior treatment included surgical resection 6 years earlier with subsequent fractionated radiation therapy and radiosurgery for tumor progression. The patient was given 5-ALA 20 mg/kg body weight dissolved in 100 mL water 3 hours before induction of anesthesia. Intraoperative fluorescence was coregistered with preoperative imaging. Neuropathological analysis of the resected falx with confocal microscopy enabled correlation of fluorescence with the extent of tumor on a histological level. Conclusion Fluorescence guidance allowed clear intraoperative delineation of tumor tissue from adjacent, uninvolved dura. On a microscopic level, there was a very close correlation of fluorescence with tumor, but some tumor cells did not fluoresce. PMID:21389893

Immunohistochemical localization of cell adhesion molecule epithelial cadherin in human arachnoid villi and meningiomas.

PubMed

Tohma, Y; Yamashima, T; Yamashita, J

1992-04-01

Cadherins are a family of intercellular glycoproteins responsible for calcium-dependent cell adhesion and are currently divided into four types: epithelial (E), neuronal (N), placental (P), and vascular (V). Since cadherins are known to be indispensable for not only morphogenesis in the embryo but also maintenance of tumor cell nest, we examined the expression of E-cadherin in 31 meningiomas (11 syncytial, 12 transitional, 8 fibroblastic) and 3 arachnoid villi by immunoblot and immunohistochemical analyses. In the immunoblot analysis, E-cadherin was detected at the main band of Mr 124,000 in all of the arachnoid villi, as well as syncytial and transitional types of meningiomas, but not in the fibroblastic type. The immunohistochemical examination showed that E-cadherin was expressed at the cell borders of syncytial and transitional types, but the expression was absent in the fibroblastic type. Immunoelectron microscopy showed that E-cadherin was localized at the intermediate junctions in arachnoid villi, while it was detected diffusely at the cell surface in meningiomas. It is suggested from these data that the expression of E-cadherin might be closely related to the differentiation and organogenesis of meningioma cells.

The Quantitative Analysis of bFGF and VEGF by ELISA in Human Meningiomas

PubMed Central

Denizot, Yves; De Armas, Rafael; Caire, François; Moreau, Jean Jacques; Pommepuy, Isabelle; Truffinet, Véronique; Labrousse, François

2006-01-01

The quantitative analysis of VEGF using ELISA in various subtypes of grade I meningiomas reported higher VEGF contents in meningothelial (2.38 ± 0.62 pg/μg protein, n = 7), transitional (1.08 ± 0.21 pg/μg protein, n = 13), and microcystic meningiomas (1.98 ± 0.87 pg/μg protein, n = 5) as compared with fibrous ones (0.36 ± 0.09 pg/μg protein, n = 5). In contrast to VEGF, no difference in the concentrations of bFGF was detected. VEGF levels did not correlate with meningioma grade (1.47 ± 0.23 pg/μg versus 2.29 ± 0.58 pg/μg for 32 and 16 grade I and II, resp), vascularisation (1.53 ± 0.41 pg/μg versus 1.96 ± 0.28 pg/μg for 24 low and 24 high vascularisated tumours, resp), and brain invasion (2.32 ± 0.59 pg/μg versus 1.46 ± 0.27 pg/μg for 7 and 41 patients with and without invasion, resp). The ELISA procedure is, thus, an interesting tool to ensure VEGF and bFGF levels in meningiomas and to test putative correlations with clinical parameters. It is, thus, tempting to speculate that ELISA would also be valuable for the quantitative analysis of other angiogenic growth factors and cytokines in intracranial tumours. PMID:17392584

Meningioma

MedlinePlus

... meningioma is a tumor that arises from the meninges — the membranes that surround your brain and spinal ... know that something alters some cells in your meninges to make them multiply out of control, leading ...

Giant Olfactory Meningiomas

PubMed Central

d'Avella, Domenico; Salpietro, Francesco M.; Alafaci, Cetty; Tomasello, Francesco

1999-01-01

Olfactory groove meningiomas may attain surprisingly large size. The subfrontal approach is currently the route preferred by most neurosurgeons for their excision. The pterional-transsylvian route represents an alternate exposure for microsurgery of frontobasal tumors. Although this approach has been already described for olfactory meningiomas, tumors of giant size were not specifically addressed in the literature. We report the application of the pterional-transsylvian approach in six patients with giant olfactory meningiomas. This series is unique because it includes only patients with tumors exceeding 6 cm in diameter with bilateral symmetrical development. A radical removal was achieved in all patients and all of them made a full recovery. To investigate the relevance of the pterional-transsylvian approach for minimizing surgical morbidity, a magnetic resonance imaging protocol was designed to characterize even subtle postoperative frontal lobe structural changes. These changes, limited to the frontal lobe ipsilateral to exposure and localized in specific anatomical domains of the prefrontal area, included cystic degenerative alterations, parenchymal gliosis, and associated persistent white matter edema. Results from the present series strengthen the usefulness of the pterional-transsylvian approach as a safe surgical route for lesions affecting the anterior skull base, even with huge bilateral symmetrical expansion, such as giant olfactory meningiomas. ImagesFigure 1Figure 2Figure 3p26-bFigure 4p27-bFigure 5Figure 6Figure 7 PMID:17171078

Neurocognition in individuals with incidentally-identified meningioma.

PubMed

Butts, Alissa M; Weigand, Stephen; Brown, Paul D; Petersen, Ronald C; Jack, Clifford R; Machulda, Mary M; Cerhan, Jane H

2017-08-01

Meningiomas are primary intracranial tumors that are often asymptomatic. To our knowledge, no study has attempted to describe neurocognitive function in patients with incidentally-discovered meningioma. We utilized the Mayo Clinic Study of Aging (MCSA), which is a population-based sample of Olmsted County, Minnesota residents that includes neuropsychological testing and brain MRI approximately every 15 months. Using a text search of radiologists' notes of 2402 MCSA individuals (mean age 77 years, scanned between 2004 and 2014) we identified 48 eligible subjects (2%) who had at least one meningioma. Most meningiomas were small (90% <3 cm). We matched each of the 48 subjects to 5 non-demented MCSA controls (n = 240) on age, sex, and education. Cognitive domains assessed included memory, attention-executive function, language, and visuospatial. More women (67%) had a meningioma than men (33%). Groups did not differ on prevalence of Mild Cognitive Impairment (Meningioma = 19%, Controls = 13%). Across cognitive domains, we observed similar performance for the two groups (p's ≥ 0.21). Subtle differences emerged in memory and language domains (p = 0.05 and p = 0.11) when we divided the Meningioma group by tumor location, wherein the small group with an infratentorial tumor performed more poorly than controls globally as well as on select memory and language measures. Our findings suggest that small meningiomas are generally cognitively benign, but that may change as the tumor evolves, and might be impacted by other factors such as meningioma location.

Expression of the tumor suppressor genes NF2, 4.1B, and TSLC1 in canine meningiomas.

PubMed

Dickinson, P J; Surace, E I; Cambell, M; Higgins, R J; Leutenegger, C M; Bollen, A W; LeCouteur, R A; Gutmann, D H

2009-09-01

Meningiomas are common primary brain tumors in dogs; however, little is known about the molecular genetic mechanisms involved in their tumorigenesis. Several tumor suppressor genes have been implicated in meningioma pathogenesis in humans, including the neurofibromatosis 2 (NF2), protein 4.1B (4.1 B), and tumor suppressor in lung cancer-1 (TSLC1) genes. We investigated the expression of these tumor suppressor genes in a series of spontaneous canine meningiomas using quantitative real-time reverse transcription polymerase chain reaction (RT-PCR) (NF2; n = 25) and western blotting (NF2/merlin, 4.1B, TSLC1; n = 30). Decreased expression of 4.1B and TSLC1 expression on western blotting was seen in 6/30 (20%) and in 15/30 (50%) tumors, respectively, with 18/30 (60%) of meningiomas having decreased or absent expression of one or both proteins. NF2 gene expression assessed by western blotting and RT-PCR varied considerably between individual tumors. Complete loss of NF2 protein on western blotting was not seen, unlike 4.1B and TSLC1. Incidence of TSLC1 abnormalities was similar to that seen in human meningiomas, while perturbation of NF2 and 4.1B appeared to be less common than reported for human tumors. No association was observed between tumor grade, subtype, or location and tumor suppressor gene expression based on western blot or RT-PCR. These results suggest that loss of these tumor suppressor genes is a frequent occurrence in canine meningiomas and may be an early event in tumorigenesis in some cases. In addition, it is likely that other, as yet unidentified, genes play an important role in canine meningioma formation and growth.

Cytological and cytogenetical studies on brain tumors. V. Preferential loss of sex chromosomes in human meningiomas.

PubMed

Zankl, H; Seidel, H; Zang, K D

1975-01-01

Twelve out of 88 cytogenetically examined meningiomas of female patients showed, in addition to the typical loss of a chromosome 22, a loss of 1 or more chromosomes of group C. Among them 8 tumors had less than 8% cells with Barr-body-like particles, whereas in one tumor 12% and in 3 others over 20% Barr bodies were found, which, based on control studies, were classified as sex-chromatin negative, partly positive, and positive, respectively. In one case the loss of an X chromosome was verified by Giemsa banding. In 6 out of 24 meningiomas of male origin, the chromosomal morphology and association pattern strongly indicated that besides the loss of a chromosome 22, the Y chromosome was also missing. Moreover, the loss of the male sex chromosome could be ascertained in 4 tumors by the conspicuous absence of Y fluorescence in interphase nuclei and in metaphase plates after fluorescence staining. The findings are discussed in connection with the gonosomal loss in other human tumors and in old age.

Rhabdoid Meningioma of Brain - A Rare Aggressive Tumor

PubMed Central

Mondal, Sajeeb; Pradhan, Rajashree; Pal, Subrata; Chatterjee, Sharmistha; Bandyapadhyay, Arindam; Bhattacharyya, Debosmita

2017-01-01

Rhabdoid meningioma is a rare aggressive variant of meningioma, regarded as WHO Grade III type. Histologically and cytologically, it is distinctive type having abundant eosinophilic cytoplasm, cytoplasmic inclusion with eccentrically placed vesicular nuclei and prominent nucleoli. High recurrence rate and poor outcome are important features. Here, we are presenting a rare case of rhabdoid meningioma found in a recurrent meningioma of the posterior fossa in a middle-aged female. We emphasized the squash cytology and histology finding of the rare neoplasm. PMID:28900335

Epilepsy and adverse quality of life in surgically resected meningioma.

PubMed

Tanti, M J; Marson, A G; Jenkinson, M D

2017-09-01

Meningiomas are common intracranial tumors, and despite surgery or therapy with anti-epileptic drugs (AEDs), many patients suffer from seizures. Epilepsy has a significant impact on quality of life (QoL) in non-tumor populations, but the impact of epilepsy on QoL in patients with meningioma is unknown. Our aim was to evaluate the impact of epilepsy on QoL in patients that have undergone resection of a benign meningioma. We recruited meningioma patients without epilepsy (n=109), meningioma patients with epilepsy (n=56), and epilepsy patients without meningioma (n=64). QoL was measured with the Short Form 36 version 2 (SF-36), the Functional Assessment of Cancer Therapy (FACT-BR), and the Liverpool Adverse Events Profile (LAEP). Regression analyses identified significant determinants of QoL. Patients with meningioma and epilepsy had poorer QoL scores than meningioma patients without epilepsy in all measures. In FACT-BR, this difference was significant. Multiple regression analyses demonstrated that current AED use had a greater impact on QoL scores than recent seizures. Other variables associated with impaired QoL included depression, unemployment, and meningioma attributed symptoms. Epilepsy has a negative impact on quality of life in patients with benign meningioma. AED use is correlated with impaired QoL and raised LAEP scores, suggesting that AEDs and adverse effects may have led to impaired QoL in our meningioma patients with epilepsy. The severity of epilepsy in our meningioma population was comparatively mild; therefore, a more conservative approach to AED therapy may be indicated in an attempt to minimize adverse effects. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Maternally expressed gene 3, an imprinted noncoding RNA gene, is associated with meningioma pathogenesis and progression.

PubMed

Zhang, Xun; Gejman, Roger; Mahta, Ali; Zhong, Ying; Rice, Kimberley A; Zhou, Yunli; Cheunsuchon, Pornsuk; Louis, David N; Klibanski, Anne

2010-03-15

Meningiomas are common tumors, representing 15% to 25% of all central nervous system tumors. NF2 gene inactivation on chromosome 22 has been shown as an early event in tumorigenesis; however, few factors underlying tumor growth and progression have been identified. The chromosomal abnormalities of 14q32 are often associated with meningioma pathogenesis and progression; therefore, it has been proposed that an as yet unidentified tumor suppressor is present at this locus. Maternally expressed gene 3 (MEG3) is an imprinted gene located at 14q32 which encodes a noncoding RNA with an antiproliferative function. We found that MEG3 mRNA is highly expressed in normal arachnoidal cells. However, MEG3 is not expressed in the majority of human meningiomas or the human meningioma cell lines IOMM-Lee and CH157-MN. There is a strong association between loss of MEG3 expression and tumor grade. Allelic loss at the MEG3 locus is also observed in meningiomas, with increasing prevalence in higher grade tumors. In addition, there is an increase in CpG methylation within the promoter and the imprinting control region of MEG3 gene in meningiomas. Functionally, MEG3 suppresses DNA synthesis in both IOMM-Lee and CH157-MN cells by approximately 60% in bromodeoxyuridine incorporation assays. Colony-forming efficiency assays show that MEG3 inhibits colony formation in CH157-MN cells by approximately 80%. Furthermore, MEG3 stimulates p53-mediated transactivation in these cell lines. Therefore, these data are consistent with the hypothesis that MEG3, which encodes a noncoding RNA, may be a tumor suppressor gene at chromosome 14q32 involved in meningioma progression via a novel mechanism.

Intracranial meningiomas related to external cranial irradiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Spallone, A.; Gagliardi, F.M.; Vagnozzi, R.

1979-08-01

Three cases are presented of meningiomas following small-dose external cranial irradiation in which several features clearly indicate a causal relationship between radiotherapy and tumor development. The length of the latent period separates meningiomas following high-dose irradiation from those which followed small-dose irradiation. Therefore the oncogenic mechanism seems to act differently in the two groups. This demonstration that multiple meningiomas can occur in patients irradiated for Tinea capitis should enable other similar cases to be recognized.

Primary extracranial meningioma of the mandible.

PubMed

Mosqueda-Taylor, Adalberto; Domínguez-Malagon, Hugo; Cano-Valdez, Ana-Maria; Montiel-Hernandez, Ana-Maria

2009-04-01

Meningiomas are benign tumors of mesodermal origin that arise from arachnoid cell clusters that penetrate the dura to form arachnoid villi. These neoplasms represent one of the most common neoplasms developing within the central nervous system and are usually located at points of entry of vessels and nerves through the dura. Extracranial meningiomas (EM) comprise only 2% of all meningiomas, and only six cases of primary EM of the jawbones have been described to date. They may arise as an extension of intracranial meningiomas or as primary tumors and may be clinically indistinguishable from other benign tumours of the jaws, as they usually present as a well-delineated unencapsulated tumors. In this article a case of primary intramandibular primary EM that appeared as a well-defined osteolytic radiolucent lesion of the jaw is reported. The salient clinico-pathological features of this case is compared to those previously reported in the literature and differential diagnosis and therapeutic considerations are discussed.

Meningiomas after cranial radiotherapy for childhood cancer: a single institution experience.

PubMed

Felicetti, Francesco; Fortunati, Nicoletta; Garbossa, Diego; Biasin, Eleonora; Rudà, Roberta; Daniele, Dino; Arvat, Emanuela; Corrias, Andrea; Fagioli, Franca; Brignardello, Enrico

2015-07-01

Childhood cancer survivors (CCS) treated with cranial radiation therapy (CRT) are at risk of developing meningiomas. The aim of this study was to evaluate the cumulative incidence of meningiomas in a cohort of CCS who previously underwent CRT. We considered all CCS who received CRT and were followed up at the "Transition Unit for Childhood Cancer Survivors" in Turin. Even though asymptomatic, they had at least one brain computed tomography or magnetic resonance imaging performed at a minimum interval of 10 years after treatment for pediatric cancer. We identified 90 patients (median follow-up 24.6 years). Fifteen patients developed meningioma (median time from pediatric cancer, 22.5 years). In four patients, it was suspected on the basis of neurological symptoms (i.e., headache or seizures), whereas all other cases, including five giant meningiomas, were discovered in otherwise asymptomatic patients. Multiple meningiomas were discovered in four CCS. Ten patients underwent surgical resection. An atypical meningioma (grade II WHO) was reported in four patients. One patient with multiple meningiomas died for a rapid growth of the intracranial lesions. A second neoplasm (SN) other than meningioma was diagnosed in five out of the 15 patients with meningioma and in ten out of the 75 CCS without meningioma. Cox multivariate analysis showed that the occurrence of meningioma was associated with the development of other SNs, whereas age, sex, or CRT dose had no influence. CCS at risk of the development of meningioma deserve close clinical follow-up, especially those affected by other SNs.

Global epigenetic profiling identifies methylation subgroups associated with recurrence-free survival in meningioma

PubMed Central

Olar, Adriana; Wani, Khalida M; Wilson, Charmaine D; Zadeh, Gelareh; DeMonte, Franco; Jones, David TW; Pfister, Stefan M; Sulman, Erik P; Aldape, Kenneth D

2017-01-01

Meningioma is the most common primary brain tumor and carries a substantial risk of local recurrence. Methylation profiles of meningioma and their clinical implications are not well understood. We hypothesized that aggressive meningiomas have unique DNA methylation patterns that could be used to better stratify patient management. Samples (n=140) were profiled using the Illumina HumanMethylation450 BeadChip. Unsupervised modeling on a training set (n=89) identified 2 molecular methylation subgroups of meningioma (MM) with significantly different recurrence free survival (RFS) times between the groups: a prognostically unfavorable subgroup (MM-UNFAV) and a prognostically favorable subgroup (MM-FAV). This finding was validated in the remaining 51 samples and led to a baseline meningioma methylation classifier (bMMC) defined by 283 CpG loci (283-bMMC). To further optimize a recurrence predictor, probes subsumed within the baseline classifier were subject to additional modeling using a similar training/validation approach, leading to a 64-CpG loci meningioma methylation predictor (64-MMP). After adjustment for relevant clinical variables [WHO grade, mitotic index, Simpson grade, sex, location, and copy number aberrations (CNA)] multivariable analyses for RFS showed that the baseline methylation classifier was not significant (p=0.0793). The methylation predictor however was significantly associated with tumor recurrence (p<0.0001). CNA were extracted from the 450k intensity profiles. Tumor samples in the MM-UNFAV subgroup showed an overall higher proportion of CNAs compared to the MM-FAV subgroup tumors and the CNAs were complex in nature. CNAs in the MM-UNFAV subgroup included recurrent losses of 1p, 6q, 14q and 18q, and gain of 1q, all of which were previously identified as indicators of poor outcome. In conclusion, our analyses demonstrate robust DNA methylation signatures in meningioma that correlate with CNAs and stratify patients by recurrence risk. PMID:28130639

Maternally Expressed Gene 3, an imprinted non-coding RNA gene, is associated with meningioma pathogenesis and progression

PubMed Central

Zhang, Xun; Gejman, Roger; Mahta, Ali; Zhong, Ying; Rice, Kimberley A.; Zhou, Yunli; Cheunsuchon, Pornsuk; Louis, David N.; Klibanski, Anne

2010-01-01

Meningiomas are common tumors, representing 15-25% of all central nervous system tumors. NF2 gene inactivation on chromosome 22 has been shown as an early event in tumorigenesis; however, few factors underlying tumor growth and progression have been identified. Chromosomal abnormalities of 14q32 are often associated with meningioma pathogenesis and progression; therefore it has been proposed that an as yet unidentified tumor suppressor is present at this locus. MEG3 is an imprinted gene located at 14q32 that encodes a non-coding RNA with an anti-proliferative function. We found that MEG3 mRNA is highly expressed in normal arachnoidal cells. However, MEG3 is not expressed in the majority of human meningiomas or the human meningioma cell lines IOMM-Lee and CH157-MN. There is a strong association between loss of MEG3 expression and tumor grade. Allelic loss at the MEG3 locus is also observed in meningiomas, with increasing prevalence in higher grade tumors. In addition, there is an increase in CpG methylation within the promoter and the imprinting control region of MEG3 gene in meningiomas. Functionally, MEG3 suppresses DNA synthesis in both IOMM-Lee and CH157-MN cells by approximately 60% in BrdU incorporation assays. Colony-forming efficiency assays show that MEG3 inhibits colony formation in CH157-MN cells by approximately 80%. Furthermore, MEG3 stimulates p53-mediated transactivation in these cell lines. Therefore, these data are consistent with the hypothesis that MEG3, which encodes a non-coding RNA, may be a tumor suppressor gene at chromosome 14q32 involved in meningioma progression via a novel mechanism. PMID:20179190

Association between prediagnostic glucose, triglycerides, cholesterol and meningioma, and reverse causality

PubMed Central

Bernardo, Brittany M; Orellana, Robert C; Weisband, Yiska Lowenberg; Hammar, Niklas; Walldius, Goran; Malmstrom, Hakan; Ahlbom, Anders; Feychting, Maria; Schwartzbaum, Judith

2016-01-01

Background: Although meningioma is a benign tumour, it may cause significant morbidity. Obesity and diabetes are positively associated with meningioma. To evaluate the potential effects of obesity-related prediagnostic glucose, triglycerides and cholesterol on meningioma and of prediagnostic meningioma on these biomarkers, we conducted a cohort study. Methods: We identified 41 355 individuals in the Apolipoprotein MOrtality RISk cohort with values for these biomarkers within 15 years before meningioma diagnosis, death, migration or the end of follow-up. We then estimated hazard ratios (HRs) and their interactions with time and age using Cox regression. Results: Meningioma was diagnosed in 181 women and 115 men whose median follow-up time was 7 years. Fasting serum glucose level was inversely related to meningioma among women (Ptrend=0.0006) but not men (Ptrend=0.24). Prediagnostic diabetes was inversely related to meningioma in both sexes combined (HR=0.45, 95% confidence interval (CI) 0.29-0.71), as was serum cholesterol within the year before diagnosis (HR=0.50, 95% CI 0.34-0.72). Conclusions: Paradoxically, hyperglycaemia is inversely associated with meningioma in women. This finding does not necessarily negate the positive role of obesity or diabetes in meningioma development; rather, it may indicate that their effects depend on the stage of development. Furthermore, the prediagnostic tumour may reduce serum cholesterol levels. PMID:27253176

Steroid hormone and epidermal growth factor receptors in meningiomas.

PubMed

Horsfall, D J; Goldsmith, K G; Ricciardelli, C; Skinner, J M; Tilley, W D; Marshall, V R

1989-11-01

A prospective study of steroid hormone and epidermal growth factor receptor expression in 57 meningiomas is presented. Scatchard analysis of radioligand binding identified 20% of meningiomas as expressing classical oestrogen receptors (ER) at levels below that normally accepted for positivity, the remainder being negative. ER could not be visualized in any meningioma using immunocytochemistry. Alternatively, 74% of meningiomas demonstrated the presence of progesterone receptors (PR) by Scatchard analysis, the specificity of which could not be attributed to glucocorticoid or androgen receptors. Confirmation of classical PR presence was determined by immunocytochemical staining. The presence of epidermal growth factor receptor (EGFR) was demonstrated in 100% of meningiomas using immunocytochemical staining. These data are reviewed in the context of previously reported results and are discussed in relation to the potential for medical therapy as an adjunct to surgery.

Long-Term Results of Gamma Knife Radiosurgery for Intracranial Meningioma

PubMed Central

Jang, Chang Ki; Jung, Hyun Ho; Chang, Jong Hee; Chang, Jin Woo; Park, Yong Gou

2015-01-01

Background The predominant treatment modality for meningioma is surgical resection. However, gamma knife radiosurgery is also an important treatment modality for meningioma that is small or cannot be completely removed because of its location. In this study, we evaluated the effectiveness and long-term results of radiosurgical treatment for meningioma in our institution. Methods We studied 628 patients (130 men and 498 women) who underwent gamma knife radiosurgery for intracranial meningioma, which is radiologically diagnosed, from Jan 2008 to Nov 2012. We included patients with single lesion meningioma, and followed up after 6 months with imaging, and then at 24 months with a clinical examination. Patients with high-grade meningioma or multiple meningiomas were excluded. We analyzed each of the factors associated with progression free survival. The median patient's age was 56.8 years. Maximal dosage was 27.8 Gy and marginal dosage was 13.9 Gy. Results The overall tumor control rate was 95%. Twenty-eight patients (4.4%) showed evidence of tumor recurrence. Ninety-eight patients (15%) developed peritumoral edema (PTE) after gamma-knife surgery; two of them (2%) underwent surgical resections due to PTE. Nine patients had craniotomy and tumor removal after gamma knife surgery. Conclusion Gamma knife surgery for intracranial meningioma has proven to be a safe and effective treatment tool with successful long-term outcomes. Gamma knife radiosurgery can be especially effective in cases of remnant meningioma after surgical resection or where PTE is not present. PMID:26605265

Long-Term Results of Gamma Knife Radiosurgery for Intracranial Meningioma.

PubMed

Jang, Chang Ki; Jung, Hyun Ho; Chang, Jong Hee; Chang, Jin Woo; Park, Yong Gou; Chang, Won Seok

2015-10-01

The predominant treatment modality for meningioma is surgical resection. However, gamma knife radiosurgery is also an important treatment modality for meningioma that is small or cannot be completely removed because of its location. In this study, we evaluated the effectiveness and long-term results of radiosurgical treatment for meningioma in our institution. We studied 628 patients (130 men and 498 women) who underwent gamma knife radiosurgery for intracranial meningioma, which is radiologically diagnosed, from Jan 2008 to Nov 2012. We included patients with single lesion meningioma, and followed up after 6 months with imaging, and then at 24 months with a clinical examination. Patients with high-grade meningioma or multiple meningiomas were excluded. We analyzed each of the factors associated with progression free survival. The median patient's age was 56.8 years. Maximal dosage was 27.8 Gy and marginal dosage was 13.9 Gy. The overall tumor control rate was 95%. Twenty-eight patients (4.4%) showed evidence of tumor recurrence. Ninety-eight patients (15%) developed peritumoral edema (PTE) after gamma-knife surgery; two of them (2%) underwent surgical resections due to PTE. Nine patients had craniotomy and tumor removal after gamma knife surgery. Gamma knife surgery for intracranial meningioma has proven to be a safe and effective treatment tool with successful long-term outcomes. Gamma knife radiosurgery can be especially effective in cases of remnant meningioma after surgical resection or where PTE is not present.

Development of patient-derived xenograft models from a spontaneously immortal low-grade meningioma cell line, KCI-MENG1.

PubMed

Michelhaugh, Sharon K; Guastella, Anthony R; Varadarajan, Kaushik; Klinger, Neil V; Parajuli, Prahlad; Ahmad, Aamir; Sethi, Seema; Aboukameel, Amro; Kiousis, Sam; Zitron, Ian M; Ebrahim, Salah A; Polin, Lisa A; Sarkar, Fazlul H; Bollig-Fischer, Aliccia; Mittal, Sandeep

2015-07-15

There is a paucity of effective therapies for recurrent/aggressive meningiomas. Establishment of improved in vitro and in vivo meningioma models will facilitate development and testing of novel therapeutic approaches. A primary meningioma cell line was generated from a patient with an olfactory groove meningioma. The cell line was extensively characterized by performing analysis of growth kinetics, immunocytochemistry, telomerase activity, karyotype, and comparative genomic hybridization. Xenograft models using immunocompromised SCID mice were also developed. Histopathology of the patient tumor was consistent with a WHO grade I typical meningioma composed of meningothelial cells, whorls, and occasional psammoma bodies. The original tumor and the early passage primary cells shared the standard immunohistochemical profile consistent with low-grade, good prognosis meningioma. Low passage KCI-MENG1 cells were composed of two cell types with spindle and round morphologies, showed linear growth curve, had very low telomerase activity, and were composed of two distinct unrelated clones on cytogenetic analysis. In contrast, high passage cells were homogeneously round, rapidly growing, had high telomerase activity, and were composed of a single clone with a near triploid karyotype containing 64-66 chromosomes with numerous aberrations. Following subcutaneous and orthotopic transplantation of low passage cells into SCID mice, firm tumors positive for vimentin and progesterone receptor (PR) formed, while subcutaneous implant of high passage cells yielded vimentin-positive, PR-negative tumors, concordant with a high-grade meningioma. Although derived from a benign meningioma specimen, the newly-established spontaneously immortal KCI-MENG1 meningioma cell line can be utilized to generate xenograft tumor models with either low- or high-grade features, dependent on the cell passage number (likely due to the relative abundance of the round, near-triploid cells). These human

Sporadic pediatric meningiomas: a neuroradiological and neuropathological study of 15 cases.

PubMed

Huntoon, Kristin; Pluto, Charles P; Ruess, Lynne; Boué, Daniel R; Pierson, Christopher R; Rusin, Jerome A; Leonard, Jeffrey

2017-08-01

OBJECTIVE Sporadic meningiomas have been classified in many different ways. Radiographically, these lesions can be described as occurring in either typical or atypical locations. The purpose of this study was to determine if there are any histopathological differences between sporadic meningiomas that arise in these varying locations in children. METHODS The neuroimaging, histopathological findings, and clinical records in patients with sporadic pediatric meningiomas not associated with neurofibromatosis Type 2 or prior radiation therapy were retrospectively reviewed. Tumors were classified by radiological findings as either typical or atypical, and they were categorized histopathologically by using the latest WHO nomenclature and grading criteria. RESULTS Fifteen sporadic meningiomas in pediatric patients were biopsied or resected at the authors' institution between 1989 and 2013. Five (33%) were typical in radiographic appearance and/or location and 10 (67%) were atypical. Four (80%) typical meningiomas were WHO Grade I tumors. Most (60%) of the atypical meningiomas were WHO Grade II or III. CONCLUSIONS This study is the largest series of sporadic pediatric meningiomas in atypical locations to date. Although sporadic meningiomas are relatively infrequent in children, those with atypical imaging, specifically those with apparently intraparenchymal and intraosseous locations, may be more common than previously recognized. In this study, pediatric sporadic meningiomas arising in atypical locations, in particular intraparenchymal meningiomas, may be of higher histopathological grade. The authors' findings should alert clinicians to the potential for more aggressive clinical behavior in these tumors.

Correlation of DNA content and nucleomorphometric features with World Health Organization grading of meningiomas.

PubMed

Grunewald, J P; Röhl, F W; Kirches, E; Dietzmann, K

1998-02-01

Many studies dealing with extracranial cancer showed a strong correlation of DNA ploidy to a poor clinical outcome, recurrence, or malignancy. In brain tumors, analysis of DNA content did not always provided significant diagnostic information. In this study, DNA density and karyometric parameters of 50 meningiomas (26 Grade I, 10 Grade II, 14 Grade III) were quantitatively evaluated by digital cell image analyses of Feulgen-stained nuclei. In particular, the densitometric parameter SEXT, which describes nuclear DNA content, as well as the morphometric values LENG (a computer-assisted measurement of nuclear circumference), AREA (a computer-assisted measurement of nuclear area), FCON (a parameter that describes nuclear roundness), and CONC (a describing nuclear contour), evaluated with the software IMAGE C, were correlated to World Health Organization (WHO) grading using univariate and multivariate methods. AREA and LENG values showed significant differences between tumors of Grades I and III. FCON values were unable to distinguish WHO Grade III from Grade I/II but were useful in clearly separating Grade II from Grade I tumors. CONC values detected differences between WHO Grades II and I/III tumors but not between the latter. SEXT values clearly distinguished Grade III from Grade I/II tumors. The 1c, 2c, 2.5c, and 5c exceeding rates showed no predictive values. Only the 6c exceeding rate showed a significant difference between Grades I and III. These results outline the characteristic features of the atypical (Grade II) meningiomas, which make them a recognizable tumor entity distinct from benign and anaplastic meningiomas. The combination of DNA densitometric and morphometric findings seems to be a powerful addition to the histopathologic classification of meningiomas, as suggested by the WHO.

Remote acute demyelination after focal proton radiation therapy for optic nerve meningioma.

PubMed

Redjal, Navid; Agarwalla, Pankaj K; Dietrich, Jorg; Dinevski, Nikolaj; Stemmer-Rachamimov, Anat; Nahed, Brian V; Loeffler, Jay S

2015-08-01

We present a unique patient with delayed onset, acute demyelination that occurred distant to the effective field of radiation after proton beam radiotherapy for an optic nerve sheath meningioma. The use of stereotactic radiotherapy as an effective treatment modality for some brain tumors is increasing, given technological advances which allow for improved targeting precision. Proton beam radiotherapy improves the precision further by reducing unnecessary radiation to surrounding tissues. A 42-year-old woman was diagnosed with an optic nerve sheath meningioma after initially presenting with vision loss. After biopsy of the lesion to establish diagnosis, the patient underwent stereotactic proton beam radiotherapy to a small area localized to the tumor. Subsequently, the patient developed a large enhancing mass-like lesion with edema in a region outside of the effective radiation field in the ipsilateral frontal lobe. Given imaging features suggestive of possible primary malignant brain tumor, biopsy of this new lesion was performed and revealed an acute demyelinating process. This patient illustrates the importance of considering delayed onset acute demyelination in the differential diagnosis of enhancing lesions in patients previously treated with radiation. Copyright © 2015 Elsevier Ltd. All rights reserved.

Radiotherapy of meningioma: a treatment in need of radiobiological research.

PubMed

Pinzi, Valentina; Bisogno, Ilaria; Prada, Francesco; Ciusani, Emilio; Fariselli, Laura

2018-05-18

Meningiomas account for one third of primary intracranial tumors, nevertheless information on meningioma cell lines and in vivo models is scant. Although radiotherapy is one of the most relevant therapeutic options for the treatment patients with meningioma, radiobiological research to understand tumor responses to this treatment is far from being thoroughly understood. The aim of this report is to provide a comprehensive picture of the current literature on this field, so as to foster s research in this regard. We carried out a review of meningioma radiobiology based on a peer-reviewed PubMed search. As a result of our study, we can confirm that the main limitation of radiobiological research into meningioma is the paucity of robust in vitro and in vivo models. Alternative approaches to overcome the already identified problems, and to allow better understanding of the entire histopathological spectrum of meningiomas have been explored. A radiobiological perspective of meningioma may help to improve clinical results both in terms of tumour control and healthy tissue sparing. Although we are far from drawing any conclusions, this review can lead researchers to identify some cues for future areas of study.

Intracranial meningiomas, the VEGF-A pathway, and peritumoral brain oedema.

PubMed

Nassehi, Damoun

2013-04-01

Meningiomas are the second-most common intracranial tumours in adults. They are derived from the arachnoid cells, and although approximately 90% of meningiomas are benign, more than half of all meningiomas develop peritumoral brain oedema (PTBE), which increases morbidity. The PTBE can be treated with steroid therapy, but this treatment is not specific, is not always effective, and involves long-term side-effects. Meningiomas are treated with radiation therapy, stereotactic radio-surgery or surgical resection. At the moment surgical resection is the only definite treatment, and the removal of the tumour also removes the PTBE. Based on the localization of the meningioma, surgery can be complicated. Although PTBE around meningiomas is frequent, the mechanisms behind its development are not clearly understood. It is believed that due to tumour growth and local tissue hypoxia, angiogenesis is increased and leads to the formation of PTBE. The angiogenic protein vascular endothelial growth factor A (VEGF-A) is believed to be involved in the formation of PTBE around meningiomas, as several studies have found that it is increased in meningiomas with PTBE. VEGF-A is also known as vascular permeability factor due to its ability to increase the permeability of capillaries. Paper I examines the VEGF-A protein and mRNA levels in 101 intracranial meningiomas. The PTBE is quantified on MRI, and capillary length and tumour water content are measured and compared to control brain tissue. Possible co-factors to PTBE like meningioma localization and subtypes are also examined. Forty-three of the patients have primary, solitary, supratentorial meningiomas with PTBE. The correlation between PTBE or edema index with the VEGF-A protein and mRNA, capillary length, and tumour water content is investigated in these patients. A novel method is used for mRNA quantification. It involves direct amplification of the mRNA with probes and branched DNA in order to produce a chemiluminescence signal

Lipid peroxidation and antioxidants status in human malignant and non-malignant thyroid tumours.

PubMed

Stanley, J A; Neelamohan, R; Suthagar, E; Vengatesh, G; Jayakumar, J; Chandrasekaran, M; Banu, S K; Aruldhas, M M

2016-06-01

Thyroid epithelial cells produce moderate amounts of reactive oxygen species that are physiologically required for thyroid hormone synthesis. Nevertheless, when they are produced in excessive amounts, they may become toxic. The present study is aimed to compare the lipid peroxidation (LPO), antioxidant enzymes - superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and non-protein thiols (reduced glutathione (GSH)) in human thyroid tissues with malignant and non-malignant disorders. The study used human thyroid tissues and blood samples from 157 women (147 diseased and 10 normal). Thyroid hormones, oxidative stress markers and antioxidants were estimated by standard methods. LPO significantly increased in most of the papillary thyroid carcinoma (PTC: 82.9%) and follicular thyroid adenoma (FTA: 72.9%) tissues, whilst in a majority of nodular goitre (69.2%) and Hashimoto's thyroiditis (HT: 73.7%) thyroid tissues, it remained unaltered. GSH increased in PTC (55.3%), remained unaltered in FTA (97.3%) and all other goiter samples studied. SOD increased in PTC (51.1%) and all other malignant thyroid tissues studied. CAT remained unaltered in PTC (95.7%), FTA (97.3%) and all other non-malignant samples (HT, MNG, TMNG) studied. GPx increased in PTC (63.8%), all other malignant thyroid tissues and remained unaltered in many of the FTA (91.9%) tissues and all other non-malignant samples (HT, MNG, TMNG) studied. In the case of non-malignant thyroid tumours, the oxidant-antioxidant balance was undisturbed, whilst in malignant tumours the balance was altered, and the change in r value observed in the LPO and SOD pairs between normal and PTC tissues and also in many pairs with multi-nodular goitre (MNG)/toxic MNG tissues may be used as a marker to differentiate/detect different malignant/non-malignant thyroid tumours. © The Author(s) 2015.

Analysis of the neurofibromatosis 2 gene reveals molecular variants of meningioma.

PubMed Central

Wellenreuther, R.; Kraus, J. A.; Lenartz, D.; Menon, A. G.; Schramm, J.; Louis, D. N.; Ramesh, V.; Gusella, J. F.; Wiestler, O. D.; von Deimling, A.

1995-01-01

There is evidence from cytogenetic and loss of heterozygosity studies for the involvement of a tumor suppressor gene on chromosome 22 in the formation of meningiomas. Recently, the NF2 gene, which causes neurofibromatosis type 2 and which is located in the affected region on chromosome 22, has been identified. A previous study on 8 of the 17 exons of the NF2 gene described mutations in 16% of meningiomas. We have analyzed the entire coding region of the NF2 gene in 70 sporadic meningiomas and identified 43 mutations in 41 patients. These resulted predominantly in immediate truncation, splicing abnormalities, or an altered reading frame of the predicted protein product. Although there was no evidence for distinct hotspots, all mutations occurred in the first 13 exons, the region of homology with the filopodial proteins moesin, ezrin, and radixin. The association of loss of heterozygosity on chromosome 22 with mutations in the NF2 gene was significant. These data suggest that NF2 represents the meningioma locus on chromosome 22. NF2 mutations occurred significantly more frequently in fibroblastic meningioma (70%) and transitional meningioma (83%) than in meningiothelial meningioma (25%), thus indicating a differential molecular pathogenesis of these meningioma variants. Images Figure 1 PMID:7717450

Computer-based radiological longitudinal evaluation of meningiomas following stereotactic radiosurgery.

PubMed

Shimol, Eli Ben; Joskowicz, Leo; Eliahou, Ruth; Shoshan, Yigal

2018-02-01

Stereotactic radiosurgery (SRS) is a common treatment for intracranial meningiomas. SRS is planned on a pre-therapy gadolinium-enhanced T1-weighted MRI scan (Gd-T1w MRI) in which the meningioma contours have been delineated. Post-SRS therapy serial Gd-T1w MRI scans are then acquired for longitudinal treatment evaluation. Accurate tumor volume change quantification is required for treatment efficacy evaluation and for treatment continuation. We present a new algorithm for the automatic segmentation and volumetric assessment of meningioma in post-therapy Gd-T1w MRI scans. The inputs are the pre- and post-therapy Gd-T1w MRI scans and the meningioma delineation in the pre-therapy scan. The output is the meningioma delineations and volumes in the post-therapy scan. The algorithm uses the pre-therapy scan and its meningioma delineation to initialize an extended Chan-Vese active contour method and as a strong patient-specific intensity and shape prior for the post-therapy scan meningioma segmentation. The algorithm is automatic, obviates the need for independent tumor localization and segmentation initialization, and incorporates the same tumor delineation criteria in both the pre- and post-therapy scans. Our experimental results on retrospective pre- and post-therapy scans with a total of 32 meningiomas with volume ranges 0.4-26.5 cm[Formula: see text] yield a Dice coefficient of [Formula: see text]% with respect to ground-truth delineations in post-therapy scans created by two clinicians. These results indicate a high correspondence to the ground-truth delineations. Our algorithm yields more reliable and accurate tumor volume change measurements than other stand-alone segmentation methods. It may be a useful tool for quantitative meningioma prognosis evaluation after SRS.

Gene expression profiles of metabolic aggressiveness and tumor recurrence in benign meningioma.

PubMed

Serna, Eva; Morales, José Manuel; Mata, Manuel; Gonzalez-Darder, José; San Miguel, Teresa; Gil-Benso, Rosario; Lopez-Gines, Concha; Cerda-Nicolas, Miguel; Monleon, Daniel

2013-01-01

Around 20% of meningiomas histologically benign may be clinically aggressive and recur. This strongly affects management of meningioma patients. There is a need to evaluate the potential aggressiveness of an individual meningioma. Additional criteria for better classification of meningiomas will improve clinical decisions as well as patient follow up strategy after surgery. The aim of this study was to determine the relationship between gene expression profiles and new metabolic subgroups of benign meningioma with potential clinical relevance. Forty benign and fourteen atypical meningioma tissue samples were included in the study. We obtained metabolic profiles by NMR and recurrence after surgery information for all of them. We measured gene expression by oligonucleotide microarray measurements on 19 of them. To our knowledge, this is the first time that distinct gene expression profiles are reported for benign meningioma molecular subgroups with clinical correlation. Our results show that metabolic aggressiveness in otherwise histological benign meningioma proceeds mostly through alterations in the expression of genes involved in the regulation of transcription, mainly the LMO3 gene. Genes involved in tumor metabolism, like IGF1R, are also differentially expressed in those meningioma subgroups with higher rates of membrane turnover, higher energy demand and increased resistance to apoptosis. These new subgroups of benign meningiomas exhibit different rates of recurrence. This work shows that benign meningioma with metabolic aggressiveness constitute a subgroup of potentially recurrent tumors in which alterations in genes regulating critical features of aggressiveness, like increased angiogenesis or cell invasion, are still no predominant. The determination of these gene expression biosignatures may allow the early detection of clinically aggressive tumors.

Intracranial meningiomas managed at Memfys hospital for neurosurgery in Enugu, Nigeria.

PubMed

Mezue, Wilfred C; Ohaegbulam, Samuel C; Ndubuisi, Chika C; Chikani, Mark C; Achebe, David S

2012-09-01

The epidemiology and pathology of meningioma in Nigeria are still evolving and little has been published about this tumor in Nigeria, especially in the southeast region. The aim of this paper is to compare the characteristics of intracranial meningioma managed in our center with the pattern reported in the literature worldwide. Retrospective analysis of prospectively recorded data of patients managed for intracranial meningioma between January 2002 and December 2010 at a Private neurosurgery Hospital in Enugu, Nigeria. We excluded patients whose histology results were inconclusive. Meningiomas constituted 23.8% of all intracranial tumors seen in the period. The male to female ratio was 1:1.1. The peak age range for males and females were in the fifth and sixth decades, respectively. The most common location is the Olfactory groove in 26.5% of patients followed by convexity in 23.5%. Presentation varied with anatomical location of tumor. Patients with olfactory groove meningioma (OGM) mostly presented late with personality changes and evidence of raised ICP. Tuberculum sellar and sphenoid region tumors presented earlier with visual impairment with or without hormonal abnormalities. Seizures occurred in 30.9% of all patients and in 45% of those with convexity meningiomas. Only 57.4% of the patients were managed surgically and there was no gender difference in this group. WHO grade1 tumors were the most common histological types occurring in 84.6%. One patient had atypical meningioma and two had anaplastic tumors. The pattern of meningioma in our area may have geographical differences in location and histology. Childhood meningioma was rare.

Association of tamoxifen with meningioma: a population-based study in Sweden

PubMed Central

Sundquist, Jan; Sundquist, Kristina

2016-01-01

Previous studies suggest that hormone therapy may play an important role in the development of meningioma. However, it is unclear whether medication with tamoxifen can prevent meningioma. Our study cohort included all women who were diagnosed with breast cancer between 1961 and 2010, and a total of 227 535 women were identified with breast cancer with a median age at diagnosis of 63 years. Women diagnosed with breast cancer after 1987 were defined as tamoxifen exposed; those diagnosed with breast cancer before or during 1987 were defined as not exposed to tamoxifen. Standardized incidence ratios (SIRs) were used to calculate the risk of subsequent meningioma. Of these women, 223 developed meningioma. For women without tamoxifen exposure, the risk of meningioma was significantly increased, with an SIR of 1.54 (95% confidence interval 1.30–1.81); the risk was not increased in those with tamoxifen exposure (SIR=1.06, 95% confidence interval 0.84–1.32). The increased risk of meningioma in women without tamoxifen exposure persisted during 10 years of follow-up. In this historical cohort study, we found that women diagnosed with breast cancer but not treated with tamoxifen had an increased incidence of meningioma, whereas the incidence was close to that of the general population in patients treated with tamoxifen. This suggests that tamoxifen may prevent the development of meningioma. PMID:25642792

Impact of radiotherapy in atypical meningioma recurrence: literature review.

PubMed

Pereira, Benedito Jamilson Araújo; de Almeida, Antônio Nogueira; Paiva, Wellingson Silva; Teixeira, Manoel Jacobsen; Marie, Suely Kazue Nagahashi

2018-03-19

Evaluate whether radiotherapy (RT) after the neurosurgical treatment of atypical meningiomas (AM) has an impact on the reduction rate of recurrence. A Medline search through October 2017 using "atypical meningioma" returned 1277 papers for initial review. Inclusion criteria were as follows. We analyzed the database and included articles in which the anatomic pathological classification of atypical meningiomas was in accordance with WHO 2007 or WHO 2016 criteria, patients > 18 years of age, and there was postoperative external beam radiation to the tumor bed. Exclusion criteria were WHO grade I or III meningioma, patients who underwent whole-brain radiation, RT used as salvage therapy for recurrence, palliative dose of RT (< 45 Gy), recurrent AMs, and multiple AMs. Papers reporting outcomes in which atypical and anaplastic meningiomas were analyzed together were rejected, as were papers with small samples that may compromise evaluation. After filtering our initial selection, only 17 papers were selected. After reviewing the seventeen articles including a total of 1761 patients (972 female and 799 male; 1.21 female/1.0 male), the difference in proportion of tumor recurrence between patients with and without radiotherapy after neurosurgical procedure was 1.0448, 95% CI [0.8318 to 1.3125], p value = 0.7062. On the basis of this review, there is no evidence to suggest that RT decreases the rate of recurrence in patients with atypical meningiomas.

Radiation-induced cerebral meningioma: a recognizable entity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rubinstein, A.B.; Shalit, M.N.; Cohen, M.L.

1984-11-01

The authors retrospectively analyzed the clinical and histopathological findings in 201 patients with intracranial meningiomas operated on in the period 1978 to 1982. Forty-three of the patients (21.4%) had at some previous time received radiation treatment to their scalp, the majority for tinea capitis. The findings in these 43 irradiated patients were compared with those in the 158 non-irradiated patients. Several distinctive clinical and histological features were identified in the irradiated group, which suggest that radiation-induced meningiomas can be defined as a separate nosological subgroup. The use of irradiation in large numbers of children with tinea capitis in the eramore » prior to the availability of griseofulvin may be responsible for a significantly increased incidence of intracranial meningiomas.« less

Epidural Cystic Spinal Meningioma

PubMed Central

Zhang, Ji; Chen, Zheng-he; Wang, Zi-feng; Sun, Peng; Jin, Jie-tian; Zhang, Xiang-heng; Zhao, Yi-ying; Wang, Jian; Mou, Yong-gao; Chen, Zhong-ping

2016-01-01

Abstract Cystic spinal meningioma (CSM) is an uncommon meningioma variant. Extradural CSMs are particularly rare and difficult to distinguish from other intraaxial tumors. This study presents a case of a 36-year-old woman with intraspinal extradual CSM at the thoracolumbar spine. She experienced persistent weakness, progressive numbness, and sensory disturbance in the right lower limb. Magnetic resonance imaging (MRI) of the patient revealed an irregular cystic mass at the thoracic 11 to lumbar 3 levels dorsally. This case was misdiagnosed as other neoplasms prior to surgery because of the atypical radiographic features and location of the tumor. Extradural CSMs should be considered in the differential diagnosis of intraspinal extradural cystic neoplasms. Complete removal of cystic wall provides an optimal outcome, rendering the lesion curable. PMID:26986119

Clinicopathologic features and pathogenesis of melanocytic colonization in atypical meningioma.

PubMed

Dehghan Harati, Mitra; Yu, Andrew; Magaki, Shino D; Perez-Rosendahl, Mari; Im, Kyuseok; Park, Young K; Bergsneider, Marvin; Yong, William H

2018-02-01

Only two prior cases of benign dendritic melanocytes colonizing a meningioma have been reported. We add a third case, describe clinicopathologic features shared by the three, and elucidate the risk factors for this very rare phenomenon. A 29 year-old Hispanic woman presented with headache and hydrocephalus. MRI showed a lobulated enhancing pineal region mass measuring 41 mm in greatest dimension. Subtotal resection of the mass demonstrated an atypical meningioma, WHO grade II, and the patient subsequently underwent radiotherapy. She presented 4 years later with diplopia, and MRI showed an enhancing extra-axial mass measuring 47 mm in greatest dimension and centered on the tentorial incisura. Subtotal resection showed a brain-invasive atypical meningioma with melanocytic colonization. The previous two cases in the literature were atypical meningiomas, one of which was also brain invasive. Atypical meningiomas may be at particular risk for melanocytic colonization as they upregulate molecules known to be chemoattractants for melanocytes. We detected c-Kit expression in a minority of the melanocytes as well as stem cell factor and basic fibroblast growth factor in the meningioma cells, suggesting that mechanisms implicated in normal melanocyte migration may be involved. In some cases, brain invasion with disruption of the leptomeningeal barrier may also facilitate migration from the subarachnoid space into the tumor. Whether there is low-level proliferation of the dendritic melanocytes is unclear. Given that all three patients were non-Caucasian, meningiomas in persons and/or brain regions with increased dendritic melanocytes may predispose to colonization. The age range spanned from 6 years old to 70 years old. All three patients were female. The role of gender and estrogen in the pathogenesis of this entity remains to be clarified. Whether melanocytic colonization may also occur in the more common Grade I meningiomas awaits identification of additional

[Diagnosis and surgical treatment of intraparenchymal sylvian fissure meningioma].

PubMed

Zheng, Jian; Wang, Shuo; Zhao, Ji-Zong; Cao, Yong

2009-09-08

To describe the characteristics of patients diagnosed with intraparenchymal sylvian meningioma at our department. A retrospective review was performed over 5 patients with intraparenchymal sylvian fissure meningioma confirmed by histopathology and receiving treatment at our department during January 1997 to September 2008. The mean age was 19.4 years old and there were 3 males and 2 females. On CT scanning, intraparenchymal sylvian meningioma was iso- or slightly hyper-dense masses. On MR imaging, tumors showed iso- or hypo- intense signal on T1WI and hyperintense signal on T2WI. After contrast enhancement, T1-weighted images revealed well-demarcated enhancing masses and intimately associated with the middle cerebral artery and its branches in the sylvian fissure. All the patients underwent craniotomy. As a rare disease with radiographic characteristics similar to those of general meningiomas, intraparenchymal sylvian fissure meningioma does not adhere to the dura matter but adhere to or even encase the middle cerebral artery and its branches in the sylvian fissure. All of the above have differential values. During the surgical procedures, a proper handling of tumor and encompassed main trunk of middle cerebral artery and its branches is crucial to patient prognosis.

MiR-34a-3p alters proliferation and apoptosis of meningioma cells in vitro and is directly targeting SMAD4, FRAT1 and BCL2

PubMed Central

Werner, Tamara V.; Hart, Martin; Nickels, Ruth; Kim, Yoo-Jin; Menger, Michael D.; Bohle, Rainer M.; Keller, Andreas; Ludwig, Nicole; Meese, Eckart

2017-01-01

Micro (mi)RNAs are short, noncoding RNAs and deregulation of miRNAs and their targets are implicated in tumor generation and progression in many cancers. Meningiomas are mostly benign, slow growing tumors of the central nervous system with a small percentage showing a malignant phenotype. Following in silico prediction of potential targets of miR-34a-3p, SMAD4, FRAT1, and BCL2 have been confirmed as targets by dual luciferase assays with co-expression of miR-34a-3p and reporter gene constructs containing the respective 3'UTRs. Disruption of the miR-34a-3p binding sites in the 3'UTRs resulted in loss of responsiveness to miR-34a-3p overexpression. In meningioma cells, overexpression of miR-34a-3p resulted in decreased protein levels of SMAD4, FRAT1 and BCL2, while inhibition of miR-34a-3p led to increased levels of these proteins as confirmed by Western blotting. Furthermore, deregulation of miR-34a-3p altered cell proliferation and apoptosis of meningioma cells in vitro. We show that SMAD4, FRAT1 and BCL2 are direct targets of miR-34a-3p and that deregulation of miR-34a-3p alters proliferation and apoptosis of meningioma cells in vitro. As part of their respective signaling pathways, which are known to play a role in meningioma genesis and progression, deregulation of SMAD4, FRAT1 and BCL2 might contribute to the aberrant activation of these signaling pathways leading to increased proliferation and inhibition of apoptosis in meningiomas. PMID:28340489

MiR-34a-3p alters proliferation and apoptosis of meningioma cells in vitro and is directly targeting SMAD4, FRAT1 and BCL2.

PubMed

Werner, Tamara V; Hart, Martin; Nickels, Ruth; Kim, Yoo-Jin; Menger, Michael D; Bohle, Rainer M; Keller, Andreas; Ludwig, Nicole; Meese, Eckart

2017-03-23

Micro (mi)RNAs are short, noncoding RNAs and deregulation of miRNAs and their targets are implicated in tumor generation and progression in many cancers. Meningiomas are mostly benign, slow growing tumors of the central nervous system with a small percentage showing a malignant phenotype.Following in silico prediction of potential targets of miR-34a-3p, SMAD4 , FRAT1 , and BCL2 have been confirmed as targets by dual luciferase assays with co-expression of miR-34a-3p and reporter gene constructs containing the respective 3'UTRs. Disruption of the miR-34a-3p binding sites in the 3'UTRs resulted in loss of responsiveness to miR-34a-3p overexpression. In meningioma cells, overexpression of miR-34a-3p resulted in decreased protein levels of SMAD4, FRAT1 and BCL2, while inhibition of miR-34a-3p led to increased levels of these proteins as confirmed by Western blotting. Furthermore, deregulation of miR-34a-3p altered cell proliferation and apoptosis of meningioma cells in vitro .We show that SMAD4 , FRAT1 and BCL2 are direct targets of miR-34a-3p and that deregulation of miR-34a-3p alters proliferation and apoptosis of meningioma cells in vitro . As part of their respective signaling pathways, which are known to play a role in meningioma genesis and progression, deregulation of SMAD4 , FRAT1 and BCL2 might contribute to the aberrant activation of these signaling pathways leading to increased proliferation and inhibition of apoptosis in meningiomas.

Hydroxyurea with or without imatinib in the treatment of recurrent or progressive meningiomas: a randomized phase II trial by Gruppo Italiano Cooperativo di Neuro-Oncologia (GICNO).

PubMed

Mazza, Elena; Brandes, Alba; Zanon, Silvia; Eoli, Marika; Lombardi, Giuseppe; Faedi, Marina; Franceschi, Enrico; Reni, Michele

2016-01-01

Hydroxyurea (HU) is among the most widely used salvage therapies in progressive meningiomas. Platelet-derived growth factor receptors are expressed in virtually all meningiomas. Imatinib sensitizes transformed cells to the cytotoxic effects of chemotherapeutic agents that interfere with DNA metabolism. The combination of HU with imatinib yielded intriguing results in recurrent malignant glioma. The current trial addressed the activity of this association against meningioma. Patients with recurrent or progressive WHO grade I-III meningioma, without therapeutic indication for surgery, radiotherapy, or stereotactic radiosurgery, aged 18-75 years, ECOG performance status 0-2, and not on enzyme-inducing anti-epileptic drugs were randomized to receive HU 500 mg BID ± imatinib 400 mg QD until progression, unacceptable toxicity, or patient's refusal. The primary endpoint was progression-free survival rate at 9 months (PFS-9). Between September 2009 and February 2012, 15 patients were randomized to receive HU + imatinib (N = 7; Arm A) or HU alone (N = 8; Arm B). Afterward the trial was prematurely closed due to slow enrollment rate. PFS-9 (A/B) was 0/75%, and median PFS was 4/19.5 months. Median and 2-year overall survival (A/B) rates were: 6/27.5 months; 28.5/75%, respectively. Main G3-4 toxicities were: G3 neutropenia in 1/0, G4 headache in 1/1, and G3 vomiting in 1/0. The conduction of a study in recurrent or progressive meningioma remains a challenge. Given the limited number of patients enrolled, no firm conclusions can be drawn about the combination of imatinib and HU. The optimal systemic therapy for meningioma failing surgery and radiation has yet to be identified.

Surgical outcomes after reoperation for recurrent skull base meningiomas.

PubMed

Magill, Stephen T; Lee, David S; Yen, Adam J; Lucas, Calixto-Hope G; Raleigh, David R; Aghi, Manish K; Theodosopoulos, Philip V; McDermott, Michael W

2018-05-04

OBJECTIVE Skull base meningiomas are surgically challenging tumors due to the intricate skull base anatomy and the proximity of cranial nerves and critical cerebral vasculature. Many studies have reported outcomes after primary resection of skull base meningiomas; however, little is known about outcomes after reoperation for recurrent skull base meningiomas. Since reoperation is one treatment option for patients with recurrent meningioma, the authors sought to define the risk profile for reoperation of skull base meningiomas. METHODS A retrospective review of 2120 patients who underwent resection of meningiomas between 1985 and 2016 was conducted. Clinical information was extracted from the medical records, radiology data, and pathology data. All records of patients with recurrent skull base meningiomas were reviewed. Demographic data, presenting symptoms, surgical management, outcomes, and complications data were collected. Kaplan-Meier analysis was used to evaluate survival after reoperation. Logistic regression was used to evaluate for risk factors associated with complications. RESULTS Seventy-eight patients underwent 100 reoperations for recurrent skull base meningiomas. Seventeen patients had 2 reoperations, 3 had 3 reoperations, and 2 had 4 or more reoperations. The median age at diagnosis was 52 years, and 64% of patients were female. The median follow-up was 8.5 years. Presenting symptoms included cranial neuropathy, headache, seizure, proptosis, and weakness. The median time from initial resection to first reoperation was 4.4 years and 4.1 years from first to second reoperation. Seventy-two percent of tumors were WHO grade I, 22% were WHO grade II, and 6% were WHO grade III. The sphenoid wing was the most common location (31%), followed by cerebellopontine angle (14%), cavernous sinus (13%), olfactory groove (12%), tuberculum sellae (12%), and middle fossa floor (5%). Forty-four (54%) tumors were ≥ 3 cm in maximum diameter at the time of the first

Clinical potential of meningioma genomic insights: a practical review for neurosurgeons.

PubMed

Karsy, Michael; Azab, Mohammed A; Abou-Al-Shaar, Hussam; Guan, Jian; Eli, Ilyas; Jensen, Randy L; Ormond, D Ryan

2018-06-01

Meningiomas are among the most common intracranial pathological conditions, accounting for 36% of intracranial lesions treated by neurosurgeons. Although the majority of these lesions are benign, the classical categorization of tumors by histological type or World Health Organization (WHO) grade has not fully captured the potential for meningioma progression and recurrence. Many targeted treatments have failed to generate a long-lasting effect on these tumors. Recently, several seminal studies evaluating the genomics of intracranial meningiomas have rapidly changed the understanding of the disease. The importance of NF2 (neurofibromin 2), TRAF7 (tumor necrosis factor [TNF] receptor-associated factor 7), KLF4 (Kruppel-like factor 4), AKT1, SMO (smoothened), PIK3CA (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha), and POLR2 (RNA polymerase II subunit A) demonstrates that there are at least 6 distinct mutational classes of meningiomas. In addition, 6 methylation classes of meningioma have been appreciated, enabling improved prediction of prognosis compared with traditional WHO grades. Genomic studies have shed light on the nature of recurrent meningioma, distinct intracranial locations and mutational patterns, and a potential embryonic cancer stem cell-like origin. However, despite these exciting findings, the clinical relevance of these findings remains elusive. The authors review the key findings from recent genomic studies in meningiomas, specifically focusing on how these findings relate to clinical insights for the practicing neurosurgeon.

Secretory meningioma: clinicopathologic features of eight cases.

PubMed

Nishio, S; Morioka, T; Suzuki, S; Hirano, K; Fukui, M

2001-07-01

The clinical and morphological features of eight patients with meningothelial meningiomas with numerous pseudopsammoma bodies (secretory meningiomas) are presented. The six female and two male patients ranged in age from 43 to 68 years. Tumours were located at the petroclival region in two, the lateral parasellar region in two, the petrous apex in one and the sphenoid ridge in three patients. On magnetic resonance imaging, they were iso or hypointense on T1-weighted images, and hyper or isointense on T 2-weighted images. Peritumoral brain edema was absent in five cases, and was mild to moderate in three cases. Serum carcinoembryonic antigen (CEA) levels were measured preoperatively in three patients, with one having an elevated serum CEA level which re turned to normal following tumour resection. Immunohistochemical analysis on the resected tumour tissues, pseudopsammoma bodies and surrounding tumour cells were shown to be CEA-positive. Ultrastructurally, pseudopsammoma bodies were composed of granular and filamentous materials located predominantly in the intracellular lumina, which were lined by microvilli. While these morphological features of focal epithelial and secretory differentiation of tumour cells call attention to the broad spectrum of differentiation properties of meningiomas, the biological behavior of the eight tumours reported herein corresponded to those of meningiomas in general. Copyright 2001 Harcourt Publishers Ltd.

Meningioma of the superior leaflet of the velum interpositum: A case report

PubMed Central

Champagne, Pierre-Olivier; Bojanowski, Michel W.

2015-01-01

Background: Meningiomas of the velum interpositum in the roof of the third ventricle are rare. Knowing from which leaflet the meningioma originates and thus its relationships with the internal cerebral and Galen veins, may help in choosing the surgical approach. Case Description: We report the case of a 40-year-old male with a meningioma arising from the superior leaflet of the velum interpositum. The tumor was resected successfully using the infratentorial-supracerebellar approach. Reviewing the literature, of the 22 reported cases of velum interpositum meningiomas, sufficient information regarding the precise location of the origin of the tumor was provided in 14 cases, all of which were from the inferior leaflet. Conclusion: We report the first case of velum interpositum meningioma arising from the superior leaflet and give a potential explanation as to why meningiomas of the velum interpositum occur more commonly on the inferior leaflet. Distinguishing from which of the two leaflets the tumor originates may influence the surgical strategy. PMID:25949856

Intratumoral heterogeneity and TERT promoter mutations in progressive/higher-grade meningiomas

PubMed Central

Juratli, Tareq A.; Thiede, Christian; Koerner, Mara V.A.; Tummala, Shilpa S.; Daubner, Dirk; Shankar, Ganesh M.; Williams, Erik A.; Martinez-Lage, Maria; Soucek, Silke; Robel, Katja; Penson, Tristan; Krause, Mechthild; Appold, Steffen; Meinhardt, Matthias; Pinzer, Thomas; Miller, Julie J.; Krex, Dietmar; Ely, Heather A.; Silverman, Ian M.; Christiansen, Jason; Schackert, Gabriele; Wakimoto, Hiroaki; Kirsch, Matthias; Brastianos, Priscilla K.; Cahill, Daniel P.

2017-01-01

Background Recent studies have reported mutations in the telomerase reverse transcriptase promoter (TERTp) in meningiomas. We sought to determine the frequency, clonality and clinical significance of telomere gene alterations in a cohort of patients with progressive/higher-grade meningiomas. Methods We characterized 64 temporally- and regionally-distinct specimens from 26 WHO grade III meningioma patients. On initial diagnoses, the meningiomas spanned all WHO grades (3 grade I, 13 grade II and 10 grade III). The tumor samples were screened for TERTp and ATRX/DAXX mutations, and TERT rearrangements. Additionally, TERTp was sequenced in a separate cohort of 19 patients with radiation-associated meningiomas. We examined the impact of mutational status on patients’ progression and overall survival. Results Somatic TERTp mutations were detected in six patients (6/26 = 23%). Regional intratumoral heterogeneity in TERTp mutation status was noted. In 4 patients, TERTp mutations were detected in recurrent specimens but not in the available specimens of the first surgery. Additionally, a TERT gene fusion (LPCAT1-TERT) was found in one sample. In contrary, none of the investigated samples harbored an ATRX or DAXX mutation. In the cohort of radiation-induced meningiomas, TERTp mutation was detected in two patients (10.5%). Importantly, we found that patients with emergence of TERTp mutations had a substantially shorter OS than their TERTp wild-type counterparts (2.7 years, 95% CI 0.9 – 4.5 years versus 10.8 years, 95% CI 7.8 -12.8 years, p=0.003). Conclusions In progressive/higher-grade meningiomas,TERTp mutations are associated with poor survival, supporting a model in which selection of this alteration is a harbinger of aggressive tumor development. In addition, we observe spatial intratumoral heterogeneity of TERTp mutation status, consistent with this model of late emergence in tumor evolution. Thus, early detection of TERTp mutations may define patients with more

Genetic changes of MLH1 and MSH2 genes could explain constant findings on microsatellite instability in intracranial meningioma.

PubMed

Pećina-Šlaus, Nives; Kafka, Anja; Bukovac, Anja; Vladušić, Tomislav; Tomas, Davor; Hrašćan, Reno

2017-07-01

Postreplicative mismatch repair safeguards the stability of our genome. The defects in its functioning will give rise to microsatellite instability. In this study, 50 meningiomas were investigated for microsatellite instability. Two major mismatch repair genes, MLH1 and MSH2, were analyzed using microsatellite markers D1S1611 and BAT26 amplified by polymerase chain reaction and visualized by gel electrophoresis on high-resolution gels. Furthermore, genes DVL3 (D3S1262), AXIN1 (D16S3399), and CDH1 (D16S752) were also investigated for microsatellite instability. Our study revealed constant presence of microsatellite instability in meningioma patients when compared to their autologous blood DNA. Altogether 38% of meningiomas showed microsatellite instability at one microsatellite locus, 16% on two, and 13.3% on three loci. The percent of detected microsatellite instability for MSH2 gene was 14%, and for MLH1, it was 26%, for DVL3 22.9%, for AXIN1 17.8%, and for CDH1 8.3%. Since markers also allowed for the detection of loss of heterozygosity, gross deletions of MLH1 gene were found in 24% of meningiomas. Genetic changes between MLH1 and MSH2 were significantly positively correlated (p = 0.032). We also noted a positive correlation between genetic changes of MSH2 and DVL3 genes (p = 0.034). No significant associations were observed when MLH1 or MSH2 was tested against specific histopathological meningioma subtype or World Health Organization grade. However, genetic changes in DVL3 were strongly associated with anaplastic histology of meningioma (χ 2  = 9.14; p = 0.01). Our study contributes to better understanding of the genetic profile of human intracranial meningiomas and suggests that meningiomas harbor defective cellular DNA mismatch repair mechanisms.

Meningioma in Down Syndrome.

PubMed

Yamamoto, Takahiro; Shinojima, Naoki; Todaka, Tatemi; Nishikawa, Shigeyuki; Yano, Shigetoshi; Kuratsu, Jun-ichi

2015-09-01

Down syndrome comprises multiple malformations and is due to trisomy of chromosome 21. There is epidemiologic evidence that individuals with Down syndrome are at decreased risk for solid tumors including brain tumors. It has been suggested that some genes expressed on the extra copy of chromosome 21 act as tumor suppressor genes and contribute to protection against tumorigenesis. We report the first case to our knowledge of a patient with Down syndrome, an 8-year-old boy, with an intracranial meningioma, in which the status of chromosome 21 was examined. The diagnosis was based on histologic examination of the surgically resected tumor. Postoperatively, the patient's neurologic status improved, and there was no tumor regrowth in the next 2 years. Fluorescence in situ hybridization for chromosome 22 confirmed high allele loss involving the neurofibromin 2 gene locus, a finding typical in meningiomas. Fluorescence in situ hybridization also revealed chromosome 21 heterogeneity in tumor cells; not only cells with trisomy 21 but also cells with disomy and monosomy 21 were present. All blood cells from the patient manifested trisomy 21. Deletion of the chromosome 21 allele may be associated with tumorigenesis of meningioma in Down syndrome. This supports the hypothesis that some genes whose expression is increased on the extra copy of chromosome 21 function as tumor suppressor genes and that they contribute to the reduced tumor incidence in individuals with Down syndrome. Copyright © 2015 Elsevier Inc. All rights reserved.

Posttranscriptional deregulation of signaling pathways in meningioma subtypes by differential expression of miRNAs.

PubMed

Ludwig, Nicole; Kim, Yoo-Jin; Mueller, Sabine C; Backes, Christina; Werner, Tamara V; Galata, Valentina; Sartorius, Elke; Bohle, Rainer M; Keller, Andreas; Meese, Eckart

2015-09-01

Micro (mi)RNAs are key regulators of gene expression and offer themselves as biomarkers for cancer development and progression. Meningioma is one of the most frequent primary intracranial tumors. As of yet, there are limited data on the role of miRNAs in meningioma of different histological subtypes and the affected signaling pathways. In this study, we compared expression of 1205 miRNAs in different meningioma grades and histological subtypes using microarrays and independently validated deregulation of selected miRNAs with quantitative real-time PCR. Clinical utility of a subset of miRNAs as biomarkers for World Health Organization (WHO) grade II meningioma based on quantitative real-time data was tested. Potential targets of deregulated miRNAs were discovered with an in silico analysis. We identified 13 miRNAs deregulated between different subtypes of benign meningiomas, and 52 miRNAs deregulated in anaplastic meningioma compared with benign meningiomas. Known and putative target genes of deregulated miRNAs include genes involved in epithelial-to-mesenchymal transition for benign meningiomas, and Wnt, transforming growth factor-β, and vascular endothelial growth factor signaling for higher-grade meningiomas. Furthermore, a 4-miRNA signature (miR-222, -34a*, -136, and -497) shows promise as a biomarker differentiating WHO grade II from grade I meningiomas with an area under the curve of 0.75. Our data provide novel insights into the contribution of miRNAs to the phenotypic spectrum in benign meningiomas. By deregulating translation of genes belonging to signaling pathways known to be important for meningioma genesis and progression, miRNAs provide a second in line amplification of growth promoting cellular signals. MiRNAs as biomarkers for diagnosis of aggressive meningiomas might prove useful and should be explored further in a prospective manner. © The Author(s) 2015. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights

A Case of Recurrent Anaplastic Meningioma of the Skull Base with Radiologic Response to Hydroxyurea

PubMed Central

Gurberg, Joshua; Bouganim, Nathaniel; Shenouda, George; Zeitouni, Anthony

2014-01-01

Anaplastic meningiomas are rare and aggressive tumors with a high propensity for local recurrence. Surgical resection and postoperative radiotherapy are the standard of care for primary disease and local recurrences. Refractory disease is managed with chemotherapy with limited success. A highly efficacious, well-tolerated chemotherapeutic agent has yet to be found for this disease entity. Hydroxyurea is currently receiving renewed attention because of its efficacy in inducing apoptosis of meningioma cells in vitro and its favorable side-effect profile. Thus far, in humans, this agent has only induced stable disease. We describe the first patient showing a near complete/partial clinical and radiological regression after 5 months of 25 mg/kg of hydroxyurea once daily, given within 1 month after stereotactic fractionated reirradiation of a previously irradiated and operated anaplastic meningioma of the skull base. Magnetic resonance imaging showed a significant and sustained response with tumor shrinkage and cavitation. PMID:25083390

Intraventricular meningiomas: a clinicopathological study and review.

PubMed

Bhatoe, Harjinder S; Singh, Prakash; Dutta, Vibha

2006-03-15

Intraventricular meningiomas are rare tumors. The origin of these tumors can be traced to embryological invagination of arachnoid cells into the choroid plexus. The authors analyzed data that they had collected to study the clinicopathological aspects and review the origin, presentation, imaging, and management of these tumors. In this retrospective analysis, the authors describe the cases of 12 patients who had received a diagnosis of intraventricular meningioma and underwent surgery for the tumors. Nine of these patients were men and three were women. Features of neurofibromatosis Type 2 were present in two of the women. Nine of the tumors were located in the lateral ventricles, one was in the third ventricle, and two were in the fourth ventricle. Raised intracranial pressure (ICP) was the universal presentation in all the patients, and the preoperative diagnoses were confirmed on neuroimaging studies. Excision was performed using the parietooccipital (trigonal) approach for lateral ventricle tumors, the transcortical-transventricular route for the third ventricle tumor, and suboccipital craniectomy for fourth ventricle tumors. Postoperatively, one patient died and the others experienced resolution of their symptoms. Histopathological features of these tumors were similar to those seen in meningiomas in other locations. Intraventricular meningiomas are slow-growing tumors that become large prior to detection. Although they are commonly seen in the lateral ventricles, they occur in the third and fourth ventricles as well. Presentation is in the form of raised ICP with no localizing features; therefore the diagnosis is based on imaging studies. Hydrocephalus occurs due to obstruction of cerebrospinal fluid pathways. Excision requires planning to avoid eloquent cortex incision. The histopathological features are varied, although most of the tumors in the study were angiomatous meningiomas. These tumors are no different histologically from tumors that are dural in

[Case of large sphenoid ridge meningioma treated by 2-stage surgery].

PubMed

Oi, Sachie; Saito, Kiyoshi; Ichikawa, Masahiro; Aimi, Yuri; Okada, Takeshi; Nagatani, Tetsuya; Shimoyama, Yoshie

2008-10-01

Large skull base meningiomas frequently encase the major cerebral vessels and cranial nerves, and receive blood supply from the branches of the internal carotid artery. One-stage resection of these tumors is difficult due to the long time needed for surgery and profuse bleeding from the tumor. We report herein a case of large sphenoid ridge atypical meningioma that was successfully resected using a combination of two-stage surgery and irradiation. A 56-year-old man was referred to us with mild left hemiparesis and visual deterioration. Computed tomography and magnetic resonance imaging showed a large sphenoid ridge meningioma. Angiography showed blood supply from the branches of both external and internal carotid arteries, and pial blood supply from the middle cerebral artery. In the first surgery after embolization of feeder vessels from the external carotid artery, the tumor was still hemorrhagic and was partially resected with 2,374 ml of blood loss. Symptoms were improved after the first surgery. Pathological diagnosis was atypical meningioma. In the second surgery after 40 Gy of irradiation, the remnant tumor was no longer hemorrhagic and was totally resected. Staged surgery with irradiation is one treatment option for large vascular skull base meningiomas, particularly for atypical meningiomas.

The Top-100 Most-Cited Articles on Meningioma.

PubMed

Almutairi, Othman; Albakr, Abdulrahman; Al-Habib, Amro; Ajlan, Abdulrazag

2017-11-01

There is an abundance of articles published on meningioma. To identify the 100 most-cited articles on meningioma and to perform a bibliometric analysis. In November 2016, we performed a title-specific search of the Scopus database using "meningioma" as our search query term without publication date restrictions. The top 100 most cited articles were obtained and reviewed. The top 100 most cited articles received a mean 198 citations per paper. Publication dates ranged from 1953 to 2013; most articles were published between 1994 and 2003, with 50 articles published during that period. NEUROSURGERY published the greatest number of top cited articles (22 of 100). The most frequent study categories were laboratorial studies (31 of 100) and natural history studies (28 of 100). Nonoperative management studies were twice as common as operative management studies in the top-cited articles. Neurosurgery as a specialty contributed to 50% of the top 100 list. The most contributing institute was the Mayo Clinic (11%); the majority of the top cited articles originated in the United States (53%). We identified the top 100 most-cited articles on meningioma that may be considered significant and impactful works, as well as the most noteworthy. In addition, we recognized the historical development and advances in meningioma research and the important contributions of various authors, specialty fields, and countries. A large proportion of the most cited articles were written by authors other than neurosurgeons, and many of these articles were published in non-neurosurgery journals. Copyright © 2017 Elsevier Inc. All rights reserved.

Foramen Magnum Meningioma: a Case Report and Review of Literature.

PubMed

Jurinovic, Pavao; Bulicic, Ana Repic; Marcic, Marino; Mise, Nikolina Ivica; Titlic, Marina; Suljic, Enra

2016-02-01

Meningiomas are slow-growing benign tumors that arise at any location where arachnoid cells reside. Although meningiomas account for a sizable proportion of all primary intracranial neoplasms (14.3-19%), only 1.8 to 3.2% arise at the foramen magnum. Their indolent development at the craniocervical junction makes clinical diagnosis complex and often leads to a long interval between onset of symptoms and diagnosis. We report a case of a 79-year-old male patient, presented with ataxia and sense of threatening fainting during verticalization. Magnetic resonance imaging revealed the presence of meningioma in the right side of craniospinal junction.

MRS study of meningeal hemangiopericytoma and edema: a comparison with meningothelial meningioma.

PubMed

Righi, Valeria; Tugnoli, Vitaliano; Mucci, Adele; Bacci, Antonella; Bonora, Sergio; Schenetti, Luisa

2012-10-01

Intracranial hemangiopericytomas (HPCs) are rare tumors and their radiological appearance resembles that of meningiomas, especially meningothelial meningiomas. To increase the knowledge on the biochemical composition of this type of tumor for better diagnosis and prognosis, we performed a molecular study using ex vivo high resolution magic angle spinning (HR-MAS) magnetic resonance spectroscopy (MRS) perfomed on HPC and peritumoral edematous tissues. Moreover, to help in the discrimination between HPC and meningothelial meningioma we compared the ex vivo HR-MAS spectra of samples from one patient with HPC and 5 patients affected by meningothelial meningioma. Magnetic resonance imaging (MRI), in vivo localized single voxel 1H-MRS was also performed on the same patients prior to surgery and the in vivo and ex vivo MRS spectra were compared. We observed the presence of OH-butyrate, together with glucose in HPC and a low amount of N-acetylaspartate in the edema, that may reflect neuronal alteration responsible for associated epilepsy. Many differences between HPC and meningothelial meningioma were identified. The relative ratios of myo-inositol, glucose and gluthatione with respect to glutamate are higher in HPC compared to meningioma; whereas the relative ratios of creatine, glutamine, alanine, glycine and choline-containing compounds with respect to glutamate are lower in HPC compared to meningioma. These data will be useful to improve the interpretation of in vivo MRS spectra resulting in a more accurate diagnosis of these rare tumors.

Long-term follow-up of 287 meningiomas in neurofibromatosis type 2 patients: clinical, radiological, and molecular features

PubMed Central

Goutagny, Stéphane; Bah, Alpha Boubacar; Henin, Dominique; Parfait, Béatrice; Grayeli, Alexis Bozorg; Sterkers, Olivier; Kalamarides, Michel

2012-01-01

Decision-making criteria for optimal management of meningiomas in neurofibromatosis type 2 (NF2) patients is hampered by lack of robust data, particularly long-term natural history. Seventy-four NF2 patients harboring 287 cranial meningiomas followed up for a mean period of 110.2 months were studied retrospectively. The median number of meningiomas per patient was 3. The mean maximum diameter of meningiomas at diagnosis was 14.3 mm, with a mean annual growth rate of 1.5 mm. Sixty-six percent of tumors showed no or minimal growth. In a subgroup of patients with 3D MRI, 7.3% of meningiomas (28% of patients) had a volumetric growth rate 20% or more per year. Twenty-five de novo meningiomas appeared during the follow-up (8.7%) and demonstrated a higher growth rate than other meningiomas (6.6 mm/year). Fifty-six meningiomas (23%) in 34 NF2 patients (45.9%) were operated on during the follow-up period. Among symptomatic resected meningiomas, grades II and III tumors were found in 29% and 6% of cases, respectively, with a remarkable intratumor histological heterogeneity. Single nucleotide polymorphism array analysis of 22 meningioma samples in 14 NF2 patients showed increasing chromosome instability with increasing grade, the most frequent losses being on 22q, 1p, 18q, and 6p. This study provides clues to improve tailored treatment of meningiomas: de novo and brain edema-associated meningiomas require active treatment. Future clinical trials in NF2 need to focus specifically on meningiomas as the primary endpoint and should include patients with meningiomas growing 20% or more per year in order to assess new treatments. PMID:22711605

Hypomethylation of DNA from Benign and Malignant Human Colon Neoplasms

NASA Astrophysics Data System (ADS)

Goelz, Susan E.; Vogelstein, Bert; Hamilton, Stanley R.; Feinberg, Andrew P.

1985-04-01

The methylation state of DNA from human colon tissue displaying neoplastic growth was determined by means of restriction endonuclease analysis. When compared to DNA from adjacent normal tissue, DNA from both benign colon polyps and malignant carcinomas was substantially hypomethylated. With the use of probes for growth hormone, γ -globin, α -chorionic gonadotropin, and γ -crystallin, methylation changes were detected in all 23 neoplastic growths examined. Benign polyps were hypomethylated to a degree similar to that in malignant tissue. These results indicate that hypomethylation is a consistent biochemical characteristic of human colonic tumors and is an alteration in the DNA that precedes malignancy.

Pittsburgh compound B (PiB) PET imaging of meningioma and other intracranial tumors.

PubMed

Johnson, Derek R; Hunt, Christopher H; Nathan, Mark A; Parisi, Joseph E; Boeve, Bradley F; Murray, Melissa E; Knopman, David S; Jack, Clifford R; Petersen, Ronald C; Lowe, Val J; Johnson, Geoffrey B

2018-01-01

Meningiomas are the most common intracranial tumors. Diagnosis by MRI is generally straightforward, but lack of imaging specificity can present a diagnostic dilemma, particularly in patients with cancer. We report our experience with meningioma identification on Pittsburgh compound B (PiB) PET/CT. Patients who underwent PiB PET/CT from 2006 to 2015 were reviewed to identify those with intracranial tumors. Tumor types were classified by MR appearance, or by pathology when available. Maximum standardized uptake value (SUVmax) measurements of tumor PiB activity were compared across tumor types. 2472 patients underwent PiB PET/CT in the period of interest; 45 patients (1.8%) had probable or definite intracranial tumor. Tumor types were meningioma (29/45, 64%), vestibular schwannoma (7/45, 16%), pituitary macroadenoma (4/45, 9%), metastatic disease (2/45, 4%), and others (3/45, 7%). In patients with meningioma, the mean lesion SUVmax was 2.05 (SD 1.37), versus 1.00 (SD 0.42) in patients with non-meningioma tumors (p < 0.01). A receiver operating curve was created for lesion:cerebellum SUVmax ratio, with an area under the curve of 0.91 for a value of 1.68. At or above this ratio, specificity for meningioma was 100% (95% CI 79-100%) and sensitivity was 76% (95% CI 57-90%). PiB PET activity within an intracranial tumor is a highly specific and reasonably sensitive marker of meningioma. Further prospective evaluation is warranted to validate this result as well as to assess the performance of commercially available beta-amyloid radiotracers in meningioma identification.

Craniocervical Junction Meningiomas without Hydrocephalus Presenting Solely with Syncope: Report of 2 Cases.

PubMed

Champagne, Pierre-Olivier; Bojanowski, Michel W

2018-06-01

To our knowledge, there have not been any reported cases of a meningioma of the craniocervical region presenting solely with syncope as its initial symptom. Only 1 case of meningioma presenting with syncope has been published, but it was associated with hydrocephalus. We report 2 cases of syncope caused by a craniocervical junction meningioma, with syncope being the sole presenting symptom and without hydrocephalus. We discuss the possible pathophysiology, as well as the clinical relevance of this type of presentation. We reviewed the charts, operative details, and imagery of 2 cases of meningioma in the region of the craniocervical junction, with syncope as their sole presenting feature. We also reviewed the literature. In 1 case the syncope occurred spontaneously. In the other, it occurred during a Valsalva maneuver. Both meningiomas were surgically removed via a retromastoid approach. There was no recurrence of syncope following surgery. Following a literature review, we found 1 case of posterior fossa meningioma presenting with syncope, but hydrocephalus was also present. Syncope can be the sole manifestation of a meningioma of the craniocervical junction. Such syncopes are a consequence of transient dysfunction of the autonomous pathways in the medulla and/or of the medulla's output. In the absence of other causes of syncope, a meningioma in this region, even in the absence of hydrocephalus, should not be considered as fortuitous, but rather as the actual cause of syncope. Recognizing this possibility offers the potential for proper diagnosis and appropriate treatment of the syncope. Copyright © 2018 Elsevier Inc. All rights reserved.

Multifocal meningiomas in a patient with a constitutional ring chromosome 22.

PubMed Central

Arinami, T; Kondo, I; Hamaguchi, H; Nakajima, S

1986-01-01

We report a patient with a constitutional ring chromosome 22, in whom multifocal meningiomas were confirmed at necropsy, and discuss the relationship between the constitutional chromosome change and tumourigenesis of meningiomas in this patient. Images PMID:3712397

DNA methylation-based classification and grading system for meningioma: a multicentre, retrospective analysis.

PubMed

Sahm, Felix; Schrimpf, Daniel; Stichel, Damian; Jones, David T W; Hielscher, Thomas; Schefzyk, Sebastian; Okonechnikov, Konstantin; Koelsche, Christian; Reuss, David E; Capper, David; Sturm, Dominik; Wirsching, Hans-Georg; Berghoff, Anna Sophie; Baumgarten, Peter; Kratz, Annekathrin; Huang, Kristin; Wefers, Annika K; Hovestadt, Volker; Sill, Martin; Ellis, Hayley P; Kurian, Kathreena M; Okuducu, Ali Fuat; Jungk, Christine; Drueschler, Katharina; Schick, Matthias; Bewerunge-Hudler, Melanie; Mawrin, Christian; Seiz-Rosenhagen, Marcel; Ketter, Ralf; Simon, Matthias; Westphal, Manfred; Lamszus, Katrin; Becker, Albert; Koch, Arend; Schittenhelm, Jens; Rushing, Elisabeth J; Collins, V Peter; Brehmer, Stefanie; Chavez, Lukas; Platten, Michael; Hänggi, Daniel; Unterberg, Andreas; Paulus, Werner; Wick, Wolfgang; Pfister, Stefan M; Mittelbronn, Michel; Preusser, Matthias; Herold-Mende, Christel; Weller, Michael; von Deimling, Andreas

2017-05-01

The WHO classification of brain tumours describes 15 subtypes of meningioma. Nine of these subtypes are allotted to WHO grade I, and three each to grade II and grade III. Grading is based solely on histology, with an absence of molecular markers. Although the existing classification and grading approach is of prognostic value, it harbours shortcomings such as ill-defined parameters for subtypes and grading criteria prone to arbitrary judgment. In this study, we aimed for a comprehensive characterisation of the entire molecular genetic landscape of meningioma to identify biologically and clinically relevant subgroups. In this multicentre, retrospective analysis, we investigated genome-wide DNA methylation patterns of meningiomas from ten European academic neuro-oncology centres to identify distinct methylation classes of meningiomas. The methylation classes were further characterised by DNA copy number analysis, mutational profiling, and RNA sequencing. Methylation classes were analysed for progression-free survival outcomes by the Kaplan-Meier method. The DNA methylation-based and WHO classification schema were compared using the Brier prediction score, analysed in an independent cohort with WHO grading, progression-free survival, and disease-specific survival data available, collected at the Medical University Vienna (Vienna, Austria), assessing methylation patterns with an alternative methylation chip. We retrospectively collected 497 meningiomas along with 309 samples of other extra-axial skull tumours that might histologically mimic meningioma variants. Unsupervised clustering of DNA methylation data clearly segregated all meningiomas from other skull tumours. We generated genome-wide DNA methylation profiles from all 497 meningioma samples. DNA methylation profiling distinguished six distinct clinically relevant methylation classes associated with typical mutational, cytogenetic, and gene expression patterns. Compared with WHO grading, classification by

Foramen Magnum Meningioma: a Case Report and Review of Literature

PubMed Central

Jurinovic, Pavao; Bulicic, Ana Repic; Marcic, Marino; Mise, Nikolina Ivica; Titlic, Marina; Suljic, Enra

2016-01-01

Introduction: Meningiomas are slow-growing benign tumors that arise at any location where arachnoid cells reside. Although meningiomas account for a sizable proportion of all primary intracranial neoplasms (14.3–19%), only 1.8 to 3.2% arise at the foramen magnum. Their indolent development at the craniocervical junction makes clinical diagnosis complex and often leads to a long interval between onset of symptoms and diagnosis. Case report: We report a case of a 79-year-old male patient, presented with ataxia and sense of threatening fainting during verticalization. Magnetic resonance imaging revealed the presence of meningioma in the right side of craniospinal junction. PMID:27041817

Differentiation of fibroblastic meningiomas from other benign subtypes using diffusion tensor imaging.

PubMed

Tropine, Andrei; Dellani, Paulo D; Glaser, Martin; Bohl, Juergen; Plöner, Till; Vucurevic, Goran; Perneczky, Axel; Stoeter, Peter

2007-04-01

To differentiate fibroblastic meningiomas, usually considered to be of a hard consistency, from other benign subtypes using diffusion tensor imaging (DTI). From DTI data sets of 30 patients with benign meningiomas, we calculated diffusion tensors and mean diffusivity (MD) and fractional anisotropy (FA) maps as well as barycentric maps representing the geometrical shape of the tensors. The findings were compared to postoperative histology. The study was approved by the local ethics committee, and informed consent was given by the patients. According to one-way analysis of variance (ANOVA), FA was the best parameter to differentiate between the subtypes (F=32.2; p<0.0001). Regarding tensor shape, endothelial meningiomas were represented by spherical tensors (80%) corresponding to isotropic diffusion, whereas the fibroblastic meningiomas showed a high percentage (43%) of nonspherical tensors, indicating planar or longitudinal diffusion. The difference was highly significant (F=28.4; p<0.0001) and may be due to the fascicular arrangement of long spindle-shaped tumor cells and the high content of intra- and interfascicular fibers as shown in the histology. In addition, a capsule-like rim of the in-plane diffusion surrounded most meningiomas irrespective of their histological type. If these results correlate to the intraoperative findings of meningioma consistency, DTI-based measurement of FA and analysis of the shape of the diffusion tensor is a promising method to differentiate between fibroblastic and other subtypes of benign meningiomas in order to get information about their "hard" or "soft" consistency prior to removal. Copyright (c) 2007 Wiley-Liss, Inc.

Genome-wide association analysis identifies a meningioma risk locus at 11p15.5.

PubMed

Claus, Elizabeth B; Cornish, Alex J; Broderick, Peter; Schildkraut, Joellen M; Dobbins, Sara E; Holroyd, Amy; Calvocoressi, Lisa; Lu, Lingeng; Hansen, Helen M; Smirnov, Ivan; Walsh, Kyle M; Schramm, Johannes; Hoffmann, Per; Nöthen, Markus M; Jöckel, Karl-Heinz; Swerdlow, Anthony; Larsen, Signe Benzon; Johansen, Christoffer; Simon, Matthias; Bondy, Melissa; Wrensch, Margaret; Houlston, Richard; Wiemels, Joseph L

2018-05-12

Meningioma are adult brain tumors originating in the meningeal coverings of the brain and spinal cord, with significant heritable basis. Genome-wide association studies (GWAS) have previously identified only a single risk locus for meningioma, at 10p12.31. To identify a susceptibility locus for meningioma, we conducted a meta-analysis of two GWAS, imputed using a merged reference panel of 1,000 Genomes and UK10K data, with validation in two independent sample series totaling 2,138 cases and 12,081 controls. We identified a new susceptibility locus for meningioma at 11p15.5 (rs2686876, odds ratio = 1.44, P = 9.86 × 10-9). A number of genes localize to the region of linkage disequilibrium encompassing rs2686876, including RIC8A, which plays a central role in the development of neural crest-derived structures, such as the meninges. This finding advances our understanding of the genetic basis of meningioma development and provides additional support for a polygenic model of meningioma.

Prostate carcinoma mimicking a sphenoid wing meningioma.

PubMed

Bradley, Lucas H; Burton, Matthew; Gokden, Murat; Serletis, Demitre

2015-01-01

We report here on a rare case of a large, lateral sphenoid wing tumor with radiographic and intraoperative findings highly suggestive of meningioma, yet pathology was in fact consistent with metastatic prostate adenocarcinoma. An 81 year-old male presented with expressive dysphasia, right-sided weakness and headaches. Imaging revealed a heterogeneously-enhancing lesion based on the left lateral sphenoid wing. The presumed diagnosis was strongly in favor of meningioma, and the patient underwent complete resection of the dural-based lesion. Final pathology confirmed the unexpected finding of a metastatic prostate adenocarcinoma. Although he tolerated surgery well, the patient was subsequently referred for palliative therapy given findings of widespread systemic disease. Intracranial metastases may involve the dura, at times presenting with rare radiographic features highly suggestive for meningioma, as in our case here. This makes differentiation, at least based on imaging, a challenge. Elderly patients presenting with neurological deficits secondary to a newly-diagnosed, dural-based lesion should thus be considered for metastasis, prompting additional imaging studies (including body CT, MRI or PET) to rule out a primary lesion elsewhere. In some cases, this may affect the overall decision to proceed with surgical resection, or alternatively, to proceed directly to palliative therapy (the latter decision made in the context of widespread metastatic disease). We conclude that dural-based metastatic lesions may mimic meningiomas, warranting thorough pre-operative work-up to exclude the possibility of metastasis. In certain cases, identification of widespread disease might preclude surgery and favor palliation, instead. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Prostate carcinoma mimicking a sphenoid wing meningioma

PubMed Central

Bradley, Lucas H.; Burton, Matthew; Gokden, Murat; Serletis, Demitre

2015-01-01

Introduction We report here on a rare case of a large, lateral sphenoid wing tumor with radiographic and intraoperative findings highly suggestive of meningioma, yet pathology was in fact consistent with metastatic prostate adenocarcinoma. Presentation of case An 81 year-old male presented with expressive dysphasia, right-sided weakness and headaches. Imaging revealed a heterogeneously-enhancing lesion based on the left lateral sphenoid wing. The presumed diagnosis was strongly in favor of meningioma, and the patient underwent complete resection of the dural-based lesion. Final pathology confirmed the unexpected finding of a metastatic prostate adenocarcinoma. Although he tolerated surgery well, the patient was subsequently referred for palliative therapy given findings of widespread systemic disease. Discussion Intracranial metastases may involve the dura, at times presenting with rare radiographic features highly suggestive for meningioma, as in our case here. This makes differentiation, at least based on imaging, a challenge. Elderly patients presenting with neurological deficits secondary to a newly-diagnosed, dural-based lesion should thus be considered for metastasis, prompting additional imaging studies (including body CT, MRI or PET) to rule out a primary lesion elsewhere. In some cases, this may affect the overall decision to proceed with surgical resection, or alternatively, to proceed directly to palliative therapy (the latter decision made in the context of widespread metastatic disease). Conclusion We conclude that dural-based metastatic lesions may mimic meningiomas, warranting thorough pre-operative work-up to exclude the possibility of metastasis. In certain cases, identification of widespread disease might preclude surgery and favor palliation, instead. PMID:26318129

Diagnosis of meningioma by time-resolved fluorescence spectroscopy.

PubMed

Butte, Pramod V; Pikul, Brian K; Hever, Aviv; Yong, William H; Black, Keith L; Marcu, Laura

2005-01-01

We investigate the use of time-resolved laser-induced fluorescence spectroscopy (TR-LIFS) as an adjunctive tool for the intraoperative rapid evaluation of tumor specimens and delineation of tumor from surrounding normal tissue. Tissue autofluorescence is induced with a pulsed nitrogen laser (337 nm, 1.2 ns) and the intensity decay profiles are recorded in the 370 to 500 nm spectral range with a fast digitizer (0.2 ns resolution). Experiments are conducted on excised specimens (meningioma, dura mater, cerebral cortex) from 26 patients (97 sites). Spectral intensities and time-dependent parameters derived from the time-resolved spectra of each site are used for tissue characterization. A linear discriminant analysis algorithm is used for tissue classification. Our results reveal that meningioma is characterized by unique fluorescence characteristics that enable discrimination of tumor from normal tissue with high sensitivity (>89%) and specificity (100%). The accuracy of classification is found to increase (92.8% cases in the training set and 91.8% in the cross-validated set correctly classified) when parameters from both the spectral and the time domain are used for discrimination. Our findings establish the feasibility of using TR-LIFS as a tool for the identification of meningiomas and enables further development of real-time diagnostic tools for analyzing surgical tissue specimens of meningioma or other brain tumors.

Diagnosis of meningioma by time-resolved fluorescence spectroscopy

PubMed Central

Butte, Pramod V.; Pikul, Brian K.; Hever, Aviv; Yong, William H.; Black, Keith L.; Marcu, Laura

2010-01-01

We investigate the use of time-resolved laser-induced fluorescence spectroscopy (TR-LIFS) as an adjunctive tool for the intraoperative rapid evaluation of tumor specimens and delineation of tumor from surrounding normal tissue. Tissue autofluorescence is induced with a pulsed nitrogen laser (337 nm, 1.2 ns) and the intensity decay profiles are recorded in the 370 to 500 nm spectral range with a fast digitizer (0.2 ns resolution). Experiments are conducted on excised specimens (meningioma, dura mater, cerebral cortex) from 26 patients (97 sites). Spectral intensities and time-dependent parameters derived from the time-resolved spectra of each site are used for tissue characterization. A linear discriminant analysis algorithm is used for tissue classification. Our results reveal that meningioma is characterized by unique fluorescence characteristics that enable discrimination of tumor from normal tissue with high sensitivity (>89%) and specificity (100%). The accuracy of classification is found to increase (92.8% cases in the training set and 91.8% in the cross-validated set correctly classified) when parameters from both the spectral and the time domain are used for discrimination. Our findings establish the feasibility of using TR-LIFS as a tool for the identification of meningiomas and enables further development of real-time diagnostic tools for analyzing surgical tissue specimens of meningioma or other brain tumors. PMID:16409091

DNA microarray analysis identifies CKS2 and LEPR as potential markers of meningioma recurrence.

PubMed

Menghi, Francesca; Orzan, Francesca N; Eoli, Marica; Farinotti, Mariangela; Maderna, Emanuela; Pisati, Federica; Bianchessi, Donatella; Valletta, Lorella; Lodrini, Sandro; Galli, Giuseppe; Anghileri, Elena; Pellegatta, Serena; Pollo, Bianca; Finocchiaro, Gaetano

2011-01-01

Meningiomas are the most frequent intracranial tumors. Surgery can be curative, but recurrences are possible. We performed gene expression analyses and loss of heterozygosity (LOH) studies looking for new markers predicting the recurrence risk. We analyzed expression profiles of 23 meningiomas (10 grade I, 10 grade II, and 3 grade III) and validated the data using quantitative polymerase chain reaction (qPCR). We performed LOH analysis on 40 meningiomas, investigating chromosomal regions on 1p, 9p, 10q, 14q, and 22q. We found 233 and 268 probe sets to be significantly down- and upregulated, respectively, in grade II or III meningiomas. Genes downregulated in high-grade meningiomas were overrepresented on chromosomes 1, 6, 9, 10, and 14. Based on functional enrichment analysis, we selected LIM domain and actin binding 1 (LIMA1), tissue inhibitor of metalloproteinases 3 (TIMP3), cyclin-dependent kinases regulatory subunit 2 (CKS2), leptin receptor (LEPR), and baculoviral inhibitor of apoptosis repeat-containing 5 (BIRC5) for validation using qPCR and confirmed their differential expression in the two groups of tumors. We calculated ΔCt values of CKS2 and LEPR and found that their differential expression (C-L index) was significantly higher in grade I than in grade II or III meningiomas (p < .0001). Interestingly, the C-L index of nine grade I meningiomas from patients who relapsed in <5 years was significantly lower than in grade I meningiomas from patients who did not relapse. These findings indicate that the C-L index may be relevant to define the progression risk in meningioma patients, helping guide their clinical management. A prospective analysis on a larger number of cases is warranted.

Temporary clamping of external carotid artery in convexity, parasagittal and temporal base meningioma.

PubMed

Yadav, Yad Ram; Parihar, Vijay; Agarwal, Moneet; Bhatele, Pushp Raj

2012-01-01

The management of intraoperative bleeding during removal of a large hyper vascular meningioma is crucial for safe and efficient surgery. Preoperative embolization of meningioma is the best way to reduce vascularity of meningiomas but this technique is not readily available, costly and has its own limitations. The study is aimed to evaluate the use of temporary clamping of external carotid artery to reduce blood loss and operating time during excision of large convexity, parasagittal or temporal base meningiomas. A prospective study of 115 consecutively operated meningiomas of size 5 cms or more were operated from January 2002 to December2010. Temporary clamping of external carotid artery was done in 61 while 51 cases were managed without clamping. There was significant reduction of blood loss, operative time and blood transfusion given in the temporary clipping group compared to non clipping group. There was stitch abscess in two patients each in clamping, and non clamping group. There was no scalp necrosis or mortality in any of the group. Temporary clamping of external carotid artery is a safe, simple and cost-effective alternative to embolization for the surgery of large meningiomas. This can be practiced at all the centers.

Boron Neutron Capture Therapy for Malignant Brain Tumors

PubMed Central

MIYATAKE, Shin-Ichi; KAWABATA, Shinji; HIRAMATSU, Ryo; KUROIWA, Toshihiko; SUZUKI, Minoru; KONDO, Natsuko; ONO, Koji

2016-01-01

Boron neutron capture therapy (BNCT) is a biochemically targeted radiotherapy based on the nuclear capture and fission reactions that occur when non-radioactive boron-10, which is a constituent of natural elemental boron, is irradiated with low energy thermal neutrons to yield high linear energy transfer alpha particles and recoiling lithium-7 nuclei. Therefore, BNCT enables the application of a high dose of particle radiation selectively to tumor cells in which boron-10 compound has been accumulated. We applied BNCT using nuclear reactors for 167 cases of malignant brain tumors, including recurrent malignant gliomas, newly diagnosed malignant gliomas, and recurrent high-grade meningiomas from January 2002 to May 2014. Here, we review the principle and history of BNCT. In addition, we introduce fluoride-18-labeled boronophenylalanine positron emission tomography and the clinical results of BNCT for the above-mentioned malignant brain tumors. Finally, we discuss the recent development of accelerators producing epithermal neutron beams. This development could provide an alternative to the current use of specially modified nuclear reactors as a neutron source, and could allow BNCT to be performed in a hospital setting. PMID:27250576

Boron Neutron Capture Therapy for Malignant Brain Tumors.

PubMed

Miyatake, Shin-Ichi; Kawabata, Shinji; Hiramatsu, Ryo; Kuroiwa, Toshihiko; Suzuki, Minoru; Kondo, Natsuko; Ono, Koji

2016-07-15

Boron neutron capture therapy (BNCT) is a biochemically targeted radiotherapy based on the nuclear capture and fission reactions that occur when non-radioactive boron-10, which is a constituent of natural elemental boron, is irradiated with low energy thermal neutrons to yield high linear energy transfer alpha particles and recoiling lithium-7 nuclei. Therefore, BNCT enables the application of a high dose of particle radiation selectively to tumor cells in which boron-10 compound has been accumulated. We applied BNCT using nuclear reactors for 167 cases of malignant brain tumors, including recurrent malignant gliomas, newly diagnosed malignant gliomas, and recurrent high-grade meningiomas from January 2002 to May 2014. Here, we review the principle and history of BNCT. In addition, we introduce fluoride-18-labeled boronophenylalanine positron emission tomography and the clinical results of BNCT for the above-mentioned malignant brain tumors. Finally, we discuss the recent development of accelerators producing epithermal neutron beams. This development could provide an alternative to the current use of specially modified nuclear reactors as a neutron source, and could allow BNCT to be performed in a hospital setting.

The Risk of Radiation-Induced Tumors or Malignant Transformation After Single-Fraction Intracranial Radiosurgery: Results Based on a 25-Year Experience

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pollock, Bruce E., E-mail: pollock.bruce@mayo.edu; Department of Radiation Oncology, Mayo Clinic College of Medicine, Rochester, Minnesota; Link, Michael J.

Purpose: To determine the risk of radiation-induced tumors or malignant transformation after single-fraction intracranial stereotactic radiosurgery (SRS). Methods and Materials: We performed a retrospective review of 1837 patients who received single-fraction SRS for arteriovenous malformation or benign tumor (meningioma, vestibular schwannoma, pituitary adenoma, glomus tumor) at a single center between 1990 and 2009. Patients were excluded if they refused research authorization (n=31), had a genetic predisposition to tumor development (n=84), received prior or concurrent radiation therapy (n=79), or had less than 5 years of imaging follow-up after SRS (n=501). The median imaging follow-up period for the remaining 1142 patients was 9.0 yearsmore » (range, 5-24.9 years). Results: No radiation-induced tumors were identified in 11,264 patient-years of follow-up after SRS. The risk of a radiation-induced tumor developing after SRS was 0.0% at 5 years (95% confidence interval [CI], 0.0%-0.4%), 0.0% at 10 years (95% CI, 0.0%-0.9%), and 0.0% at 15 years (95% CI, 0.0%-2.8%). Malignant transformation occurred in 7 of 316 meningioma patients (2.2%) and 1 of 358 vestibular schwannoma patients (0.3%) at a median of 4.9 years (range, 2.8-13.8 years) after SRS. No cases of malignant transformation were noted in patients with pituitary adenomas (n=188) or glomus tumors (n=47). The 5-, 10-, and 15-year risk of malignant transformation was 0.5% (95% CI, 0.0%-0.9%), 0.8% (95% CI, 0.0%-1.8%), and 2.4% (95% CI, 0.0%-5.5%), respectively. Patients who underwent prior resection (hazard ratio, 14.56; 95% CI, 1.79-118.33; P=.01) and who had meningioma pathology (hazard ratio, 11.72; 95% CI, 1.44-96.15; P=.02) were at increased risk of malignant transformation. Conclusions: The risk of radiation-induced tumors or malignant transformation after SRS is very low and should not be used as a justification for choosing alternative treatment approaches (surgical resection, observation

Reduced Allergy and Immunoglobulin E among Adults with Intra-cranial Meningioma Compared to Controls

PubMed Central

Wiemels, Joseph L.; Wrensch, Margaret; Sison, Jennette D.; Zhou, Mi; Bondy, Melissa; Calvocoressi, Lisa; Black, Peter M.; Yu, Herbert; Schildkraut, Joellen M.; Claus, Elizabeth B.

2012-01-01

Meningioma, the most frequent tumor in the central nervous system, has few recognized risk factors. We explored the role of allergies in a population-based case-control consortium study of meningioma in five geographic areas. We also studied serum levels of a marker of atopic allergy (IgE) in a subset of study participants, a first for a study on meningioma. Participants (N = 1,065) with surgically resected, pathologically confirmed meningioma and controls (N = 634) selected via random-digit dialing were recruited and interviewed. Cases were less likely than controls to report history of physician-diagnosed allergy [odds ratio (OR) = 0.64; 95% confidence interval (95% CI): 0.51 – 0.80]. Also, cases (N = 295) had lower total serum IgE than controls [N = 192; OR = 0.85, 95% CI: 0.75–0.98 for each unit of Ln(IgE)]. Similar to glioma and cancers at several other sites, meningioma appears to have an inverse relationship with history of allergies and a biomarker of atopic allergy. Since some common opposing predisposition or developmental processes for allergy and meningioma may exist, further research into immune processes that can affect the incidence and natural history of meningioma is warranted. PMID:21520030

Superior interhemispheric approach for midline meningioma from the anterior cranial base.

PubMed

Lévêque, S; Derrey, S; Martinaud, O; Gérardin, E; Langlois, O; Fréger, P; Hannequin, D; Castel, H; Proust, F

2011-07-01

For suprasellar meningioma, the fronto-basal exposure is considered the standard approach. The superior interhemispheric (IH) approach is less described in the literature. To assess the surgical complications, functional outcome (visual, olfaction), morbidity and mortality rates and late recurrence, after resection by superior IH approach of midline skull base meningioma. Between 1998 and 2008, 52 consecutive patients with midline meningioma on the anterior portion of the skull base (mean age: 63.8 ± 13.1; sex ratio F/M: 3.7) were operated on via the superior IH approach. After a mean follow-up of 56.9 ± 32.9 months, an independent neurosurgeon proposed a prospective examination of functional outcome to each patient, as well as a visual and olfactory function assessment. Fifty-two patients were divided into a group with olfactory groove meningioma (n=34) and another with tuberculum sellae meningioma (n=18). The outcome was characterized by postoperative complications in 13 patients (25%), mortality rate in two (3.8%) and long-term morbidity at in 17 (37%) of 50 surviving patients. Based on multivariate analysis, no prognosis factor was significant as regards the favorable outcome. The mean postoperative KPS score (86.6 ± 9.4) was significantly improved. However, dysexecutive syndrome was observed in four patients (8%), hyposmia-anosmia in 34 (68%) and visual acuity deteriorated in one (2%). The superior IH approach could be considered a safe anteriorly orientated midline approach for removal OGM and TSM meningioma. Copyright © 2011. Published by Elsevier Masson SAS.

Tumor initiation in human malignant melanoma and potential cancer therapies.

PubMed

Ma, Jie; Frank, Markus H

2010-02-01

Cancer stem cells (CSCs), also known as tumor-initiating cells, have been identified in several human malignancies, including human malignant melanoma. The frequency of malignant melanoma-initiating cells (MMICs), which are identified by their expression of ATP-binding cassette (ABC) family member ABCB5, correlates with disease progression in human patients. Furthermore, targeted MMIC ablation through ABCB5 inhibits tumor initiation and growth in preclinical xenotransplantation models, pointing to potential therapeutic promise of the CSC concept. Recent advances also show that CSCs can exert pro-angiogenic roles in tumor growth and serve immunomodulatory functions related to the evasion of host anti-tumor immunity. Thus, MMICs might initiate and sustain tumorigenic growth not only as a result of CSC-intrinsic self-renewal, differentiation and proliferative capacity, but also based on pro-tumorigenic interactions with the host environment.

Tumor Initiation in Human Malignant Melanoma and Potential Cancer Therapies

PubMed Central

Ma, Jie; Frank, Markus H.

2010-01-01

Cancer stem cells (CSCs), also known as tumor-initiating cells, have been identified in several human malignancies, including human malignant melanoma. The frequency of malignant melanoma-initiating cells (MMICs), which are identified by their expression of ATP-binding cassette (ABC) family member ABCB5, correlates with disease progression in human patients. Furthermore, targeted MMIC ablation through ABCB5 inhibits tumor initiation and growth in preclinical xenotransplantation models, pointing to potential therapeutic promise of the CSC concept. Recent advances also show that CSCs can exert pro-angiogenic roles in tumor growth and serve immunomodulatory functions related to the evasion of host anti-tumor immunity. Thus, MMICs might initiate and sustain tumorigenic growth not only as a result of CSC-intrinsic self-renewal, differentiation and proliferative capacity, but also based on pro-tumorigenic interactions with the host environment. PMID:20184545

DNA Microarray Analysis Identifies CKS2 and LEPR as Potential Markers of Meningioma Recurrence

PubMed Central

Menghi, Francesca; Orzan, Francesca N.; Eoli, Marica; Farinotti, Mariangela; Maderna, Emanuela; Pisati, Federica; Bianchessi, Donatella; Valletta, Lorella; Lodrini, Sandro; Galli, Giuseppe; Anghileri, Elena; Pellegatta, Serena; Pollo, Bianca

2011-01-01

Meningiomas are the most frequent intracranial tumors. Surgery can be curative, but recurrences are possible. We performed gene expression analyses and loss of heterozygosity (LOH) studies looking for new markers predicting the recurrence risk. We analyzed expression profiles of 23 meningiomas (10 grade I, 10 grade II, and 3 grade III) and validated the data using quantitative polymerase chain reaction (qPCR). We performed LOH analysis on 40 meningiomas, investigating chromosomal regions on 1p, 9p, 10q, 14q, and 22q. We found 233 and 268 probe sets to be significantly down- and upregulated, respectively, in grade II or III meningiomas. Genes downregulated in high-grade meningiomas were overrepresented on chromosomes 1, 6, 9, 10, and 14. Based on functional enrichment analysis, we selected LIM domain and actin binding 1 (LIMA1), tissue inhibitor of metalloproteinases 3 (TIMP3), cyclin-dependent kinases regulatory subunit 2 (CKS2), leptin receptor (LEPR), and baculoviral inhibitor of apoptosis repeat-containing 5 (BIRC5) for validation using qPCR and confirmed their differential expression in the two groups of tumors. We calculated ΔCt values of CKS2 and LEPR and found that their differential expression (C-L index) was significantly higher in grade I than in grade II or III meningiomas (p < .0001). Interestingly, the C-L index of nine grade I meningiomas from patients who relapsed in <5 years was significantly lower than in grade I meningiomas from patients who did not relapse. These findings indicate that the C-L index may be relevant to define the progression risk in meningioma patients, helping guide their clinical management. A prospective analysis on a larger number of cases is warranted. PMID:21948653

Olfactory groove meningiomas: approaches and complications.

PubMed

Aguiar, Paulo Henrique Pires de; Tahara, Adriana; Almeida, Antonio Nogueira; Simm, Renata; Silva, Arnaldo Neves da; Maldaun, Marcos Vinicius Calfatt; Panagopoulos, Alexandros Theodoros; Zicarelli, Carlos Alexandre; Silva, Pedro Gabriel

2009-09-01

Olfactory groove meningiomas (OGM) account for 4.5% of all intracranial meningiomas. We report 21 patients with OGMs. Tumors were operated on using three surgical approaches: bifrontal (7 patients), fronto-pterional (11 patients) and fronto-orbital (3 patients). Total tumor removal (Simpson Grade 1) was achieved in 13 patients and Simpson II in 8 patients. Perioperative mortality was 4.76%. The average size of the OGM was 4.3+/-1.1cm. The overall recurrence rate was 19%. We preferred to use the pterional approach, which provides quick access to the tumor with less brain exposure. It also allows complete drainage of cisternal cerebrospinal fluid, providing a good level of brain relaxation during surgery. However, for long, thin tumors, hemostasis can be difficult using this approach.

The transcondylar approach to craniocervical meningiomas.

PubMed

Rassi, Marcio S; de Oliveira, Jean G; Borba, Luis A B

2017-10-01

Surgical removal of foramen magnum meningiomas poses great challenges due their deep location within the central skull base and their proximity to vital neurovascular structures. This video depicts the operative nuances of surgical management for a 59-year-old female who presented with a right-sided spinocranial meningioma. Simpson Grade I resection was achieved through a right transcondylar approach. The patient's postoperative period was unremarkable, and she was discharged home on postoperative Day 5 for periodic follow-up. The transcondylar approach safely exposes the craniocervical junction at the anterior aspect of the neuraxis and still allows the surgeon to access the tumor through a parallel plane, with minimum morbidity. The video can be found here: https://youtu.be/P0-kXjAkw9U .

Primary intraosseous atypical inflammatory meningioma presenting as a lytic skull lesion: Case report with review of literature.

PubMed

Bohara, Sangita; Agarwal, Swapnil; Khurana, Nita; Pandey, P N

2016-01-01

Primary extradural meningiomas of the skull comprise 1% of all meningiomas, and lytic skull meningiomas are still rarer and are said to be more aggressive. We present a case of 38-year-old male with an extradural tumor which on histopathological examination showed features of inflammatory atypical meningioma (WHO Grade II). The intense inflammatory nature of osteolytic primary intraosseous meningioma has not been reported before. This entity deserves special mention because of the need for adjuvant therapy and proper follow-up.

The Role of Mifepristone in Meningiomas Management: A Systematic Review of the Literature.

PubMed

Cossu, Giulia; Levivier, Marc; Daniel, Roy Thomas; Messerer, Mahmoud

2015-01-01

We performed a systematic literature review to analyze the clinical application and the safety of mifepristone, a prominent antiprogesterone agent, in meningioma patients. A systematic search was performed through Medline, Cochrane, and clinicaltrials.gov databases from 1960 to 2014. Study Selection. Studies were selected through a PICO approach. Population was meningioma patients, meningioma cells cultures, and animal models. Intervention was mifepristone administration. Control was placebo administration or any other drug tested. Outcomes were clinical and radiological responsiveness, safety profile, and cell growth inhibition. A total of 7 preclinical and 6 clinical studies and one abstract were included. Encouraging results were found in preclinical studies. Concerning clinical studies, the response rate to mifepristone in terms of radiological regression and symptomatic improvement/stability in patients with inoperable meningioma was low. In meningiomatosis, favorable preliminary results were recorded. The safety profile was good. Limitations were as follows. The tumoral expression of progesterone receptors was not analyzed systematically in every study considered. No clear evidence exists to recommend mifepristone in inoperable meningiomas. Preliminary encouraging results were found in diffuse meningiomatosis. Mifepristone is a well-tolerated treatment. Patients' selection and hormonal profile analysis in meningiomas are fundamental for a better understanding of its benefit. Multicenter placebo-controlled trials are required.

Coincidental Optic Nerve Meningioma and Thyroid Eye Disease.

PubMed

Garg, Aakriti; Patel, Payal; Lignelli, Angela; Baron, Edward; Kazim, Michael

2015-01-01

A 57-year-old woman with diabetes mellitus, hypertension, obesity, and Graves disease presented with clinical evidence of thyroid eye disease (TED) and optic neuropathy. She was referred when a tapered dose of steroids prompted worsening of her TED. CT and MRI were consistent with TED and bilateral optic nerve meningioma. To the authors' knowledge, this is the first reported case of concurrent TED and unsuspected bilateral optic nerve meningioma. When investigating the etiology of TED-associated optic neuropathy, careful attention to orbital imaging is required because coexisting pathology may exist.

Preoperative Embolization of Skull Base Meningiomas: Outcomes in the Onyx Era.

PubMed

Przybylowski, Colin J; Baranoski, Jacob F; See, Alfred P; Flores, Bruno C; Almefty, Rami O; Ding, Dale; Chapple, Kristina M; Sanai, Nader; Ducruet, Andrew F; Albuquerque, Felipe C

2018-05-09

Preoperative embolization may facilitate skull base meningioma resection, but its safety and efficacy in the Onyx era have not been investigated. In this retrospective cohort study, we evaluated the outcomes of preoperative embolization of skull base meningiomas using Onyx as the primary embolysate. We queried an endovascular database for patients with skull base meningiomas who underwent preoperative embolization at our institution in 2007-2017. Patient, tumor, procedure, and outcome data were analyzed. Twenty-eight patients (28 meningiomas) underwent successful preoperative meningioma embolization. The mean patient age ± SD was 56 ± 13 years, and 18 patients (64%) were women. The mean tumor size was 49 cm 3 . There were 1, 2, or 3 arterial pedicles embolized in 21 cases (75%), 6 cases (21%), and 1 case (4%), respectively. The embolized pedicles included branches of the middle meningeal artery in 19 cases (68%), the internal maxillary artery in 8 cases (29%), the ascending pharyngeal artery in 2 cases (7%), and the posterior auricular, ophthalmic, occipital, and anterior cerebral arteries in 1 case each (4%). The embolysates used were Onyx alone in 20 cases (71%), n-butyl cyanoacrylate alone in 3 cases (11%), coils/particles and Onyx/n-butyl cyanoacrylate in 2 cases each (7%), and Onyx and coils in 1 case (4%). The median degree of tumor devascularization was 60%. Significant neurologic morbidity occurred in 1 patient (4%) who developed symptomatic peritumoral edema after Onyx embolization. For appropriately selected skull base meningiomas supplied by dura mater-based arterial pedicles without distal cranial nerve supply, preoperative embolization with current embolysate technology affords substantial tumor devascularization with a low complication rate. Copyright © 2018 Elsevier Inc. All rights reserved.

Cervico-occipital meningioma in a 5-year-old child: a case report.

PubMed

Ben Nsir, Atef; Boubaker, Adnene; Jemel, Hafedh

2014-01-01

Childhood meningiomas are scarce in clinical practice with an incidence ranging from 0.4 to 4.6% of all pediatric central nervous system (CNS) tumors. Cervico-occipital meningiomas account for 3.7% of childhood meningiomas and are slightly more frequent in male. A 5-year-old female presented with febrile posterior cervico-occipital pain for 3 weeks. She was diagnosed with meningitis and treated for a similar period with adapted antibiotics. The pain persisted even after treatment. Magnetic resonance imaging revealed an enhancing subdural extra medullary mass of the cervico occipital junction, developing around the left vertebral artery. The characteristics of the lesion were strongly suggestive of a neuroma. Surgical removal of the tumor aiming the decompression of the spinal cord and nerve roots was performed with a surprising discovery: The tumor was tightly attached to the dura at the entry of the left vertebral artery. The resection was total and only a thin part close to the artery was left. The pathological findings confirmed the diagnosis of meningothelial meningioma. Meningioma should be considered in the differential diagnosis of contrast enhancing subdural extra medullary lesions of the cervico-occipital junction in children.

The historical origin of the term "meningioma" and the rise of nationalistic neurosurgery.

PubMed

Barthélemy, Ernest Joseph; Sarkiss, Christopher A; Lee, James; Shrivastava, Raj K

2016-11-01

The historical origin of the meningioma nomenclature unravels interesting social and political aspects about the development of neurosurgery in the late 19th century. The meningioma terminology itself was the subject of nationalistic pride and coincided with the advancement in the rise of medicine in Continental Europe as a professional social enterprise. Progress in naming and understanding these types of tumor was most evident in the nations that successively assumed global leadership in medicine and biomedical science throughout the 19th and 20th centuries, that is, France, Germany, and the United States. In this vignette, the authors delineate the uniqueness of the term "meningioma" as it developed within the historical framework of Continental European concepts of tumor genesis, disease states, and neurosurgery as an emerging discipline culminating in Cushing's Meningiomas text. During the intellectual apogee of the French Enlightenment, Antoine Louis published the first known scientific treatise on meningiomas. Like his father, Jean-Baptiste Louis, Antoine Louis was a renowned military surgeon whose accomplishments were honored with an admission to the Académie royale de chirurgie in 1749. His treatise, Sur les tumeurs fongueuses de la duremère, appeared in 1774. Following this era, growing economic depression affecting a frustrated bourgeoisie triggered a tumultuous revolutionary period that destroyed France's Ancien Régime and abolished its university and medical systems. The resulting anarchy was eventually quelled through legislation aiming to satisfy Napoleon's need for qualified military professionals, including physicians and surgeons. These laws laid the foundations for the subsequent flourishing of French medicine throughout the mid-19th century. Subsequent changes to the meningioma nomenclature were authored by intellectual giants of this postrevolutionary period, for example, by the Limogesborn pathologist Jean Cruveilhier known for the term

The identification of factors affecting intracranial meningioma recurrence two years postoperatively

NASA Astrophysics Data System (ADS)

Iskandar, M. M.; Aman, R. A.; Tjahjadi, H.; Safri, A. Y.; Aninditha, T.

2017-08-01

The study objective was to determine the recurrence rate of intracranial meningioma and the risk factors that are contributory to an increase in the incidence of recurrence. A prospective design was used in this study on meningioma patients treated at Cipto Mangunkusumo Hospital between 2010 and mid-2015. Data on the subjects were collected from the Departments of Neurology, Neurology, and Pathology, at the Universitas Indonesia/Cipto Mangunkusumo Hospital. The subjects were adults who had been previously diagnosed with meningioma. Follow-up was performed to assess the patients in relation to their initial clinical presentation. Neuroimaging was carried out to determine recurrence. The histopathological findings, extent of tumor resection (using Simpson’s criteria), and Word Health Organization grade, were also determined. Immunohistochemistry was performed to evaluate the expression of progesterone receptor (PR), Ki-67, and vascular endothelial growth factor (VEGF). The recurrence rate was then analyzed to determine any correlation with the aforementioned risk factors. The recurrence rate was found to be 13%. Ki67, VEGF, and PR expression was positive in 9%, 73%, and 50% of the subjects, respectively. A significant correlation was not found between the study variables (tumor location, the scope of resection based on Simpson’s criteria, histopathologic grade, mitotic index, i.e., Ki-67, and PR and VEGF expression in the meningioma tissue) and the recurrence of meningioma.

Hemoglobin enhances tissue factor expression on human malignant cells.

PubMed

Siddiqui, F A; Amirkhosravi, A; Amaya, M; Meyer, T; Biggerstaff, J; Desai, H; Francis, J L

2001-04-01

Tissue Factor (TF) is a transmembrane glycoprotein that complexes with factor VII/activated factor VII to initiate blood coagulation. TF may be expressed on the surface of various cells including monocytes and endothelial cells. Over-expression of TF in human tumor cell lines promotes metastasis. We recently showed that hemoglobin (Hb) forms a specific complex with TF purified from human malignant melanoma cells and enhances its procoagulant activity (PCA). To further study this interaction, we examined the effect of Hb on the expression of TF on human malignant (TF+) cells and KG1 myeloid leukemia (TF-) cells. Human melanoma A375 and J82 bladder carcinoma cells, which express TF at moderate and relatively high levels, respectively, were incubated with varying concentrations (0-1.5 mg/ml) of Hb. After washing, cells were analyzed for Hb binding and TF expression using flow cytometry and confocal microscopy. Hb bound to the cells in a concentration-dependent manner, and increased both TF expression and PCA. The human A375 malignant melanoma cells incubated with Hb (1 mg/ml) expressed up to six times more TF antigen than cells without Hb. This increase in TF expression and PCA of intact cells incubated with Hb was significantly inhibited by cycloheximide at a concentration of 10 microg/ml (P < 0.01). An increase in total cellular TF antigen content was demonstrated by specific immunoassay. In contrast, Hb (5 mg/ml) did not induce TF expression and PCA on KG1 cells as determined by flow cytometry and TF (FXAA) activity. We conclude that Hb specifically binds to TF-bearing malignant cells and increases their PCA. This effect seems to be at least partly due to de novo synthesis of TF and increased surface expression. However, the exact mechanism by which Hb binds and upregulates TF expression remains to be determined.

Association of Genetic Predisposition With Solitary Schwannoma or Meningioma in Children and Young Adults.

PubMed

Pathmanaban, Omar N; Sadler, Katherine V; Kamaly-Asl, Ian D; King, Andrew T; Rutherford, Scott A; Hammerbeck-Ward, Charlotte; McCabe, Martin G; Kilday, John-Paul; Beetz, Christian; Poplawski, Nicola K; Evans, D Gareth; Smith, Miriam J

2017-09-01

Meningiomas and schwannomas are usually sporadic, isolated tumors occurring in adults older than 60 years and are rare in children and young adults. Multiple schwannomas and/or meningiomas are more frequently associated with a tumor suppressor syndrome and, accordingly, trigger genetic testing, whereas solitary tumors do not. Nevertheless, apparently sporadic tumors in young patients may herald a genetic syndrome. To determine the frequency of the known heritable meningioma- or schwannoma-predisposing mutations in children and young adults presenting with a solitary meningioma or schwannoma. Using the database of the Manchester Centre for Genomic Medicine, this cohort study analyzed lymphocyte DNA from young individuals prospectively referred to the clinic for genetic testing between January 1, 1990, and December 31, 2016, on presentation with a single meningioma (n = 42) or schwannoma (n = 135) before age 25 years. Sequencing data were also examined from an additional 39 patients with neurofibromatosis type 2 who were retrospectively identified as having a solitary tumor before age 25 years. Patients with schwannoma were screened for NF2, SMARCB1, and LZTR1 gene mutations, while patients with meningioma were screened for NF2, SMARCB1, SMARCE1, and SUFU. The type of underlying genetic mutation, or lack of a predisposing mutation, was associated with the presenting tumor type and subsequent development of additional tumors or other features of known schwannoma- and meningioma-predisposing syndromes. In 2 cohorts of patients who presented with an isolated meningioma (n = 42; median [range] age, 11 [1-24] years; 22 female) or schwannoma (n = 135; median [range] age, 18 [0.2-24] years; 60 female) before age 25 years, 16 of 42 patients (38%) had a predisposing mutation to meningioma and 27 of 135 patients (20%) to schwannoma, respectively. In the solitary meningioma cohort, 34 of 63 patients (54%) had a constitutional mutation in a known meningioma

Studies of the endothelial origin of cells in systemic angioendotheliomatosis and other vascular lesions of the brain and meninges using ulex europaeus lectin stains.

PubMed

Schelper, R L; Olson, S P; Carroll, T J; Hart, M N; Witters, E

1986-01-01

Ulex europaeus agglutinin I (UEA-I) is a plant lectin which binds specifically to alpha-L-fucose moieties on the surface glycoproteins of human endothelial cells. The binding is completely inhibited by preincubation of the lectin with fucose. UEA-I can be conjugated directly to fluorescein or peroxidase and can be used to stain endothelium of paraffin embedded tissues. UEA-I staining was evaluated on normal and infarcted brain, systemic angioendotheliomatosis, metastatic epidural angiosarcoma, hemangioendothelioma, hemangioblastoma, angioblastic meningioma of both the hemangioblastic and hemangiopericytic types, and vascular meningioma. The endothelium, but not neuropil of normal and infarcted brain was positive for UEA-I. The tumor cells of hemangioendothelioma and angiosarcoma also stained. However, no staining was seen in malignant intravascular cells of angioendotheliomatosis, the stromal cells of hemangioblastoma, or pericytes of angioblastic meningioma. It is concluded that the malignant cells in angioendotheliomatosis, the stromal cells of hemangioblastoma and the pericytes of angioblastic meningioma do not produce surface glycoproteins characteristic of endothelial cells.

CYR61 suppresses growth of human malignant melanoma.

PubMed

Chen, Jun; Liu, Yang; Sun, Qilin; Wang, Beiqing; Li, Ningli; Chen, Xiangdong

2016-11-01

Cysteine-rich protein 61 (CCN1/CYR61) is an important marker of proliferation and metastasis in malignant melanoma, making it a potential target for melanoma treatment. In this study, we compared the expression of CRY61 in Chinese patients with malignant melanoma with its expression in patients with other skin tumors or with no skin pathological conditions. We examined the effects of anti-human CYR61 monoclonal antibody on proliferation and evaluated the changes in CYR61 expression and cell proliferation in response to treatment with either epirubicin or interferon (IFN)-α. CYR61 was expressed at lower levels in patients with malignant melanoma than in patients with other skin tumors or with no pathology. Following the treatment of B16 cells with epirubicin and IFN-α, CYR61 levels increased, cell growth was inhibited, and proliferating cell nuclear antigen expression decreased. Thus, CYR61 could become a therapeutic target for malignant melanoma patients with high CYR61 expression.

Does Histologic Subtype Influence the Post-Operative Outcome in Spinal Meningioma?

PubMed Central

Zham, Hanieh; Moradi, Afshin; Rakhshan, Azadeh; Zali, Alireza; Rahbari, Ali; Raee, Mohammadreza; Ashrafi, Farzad; Ahadi, Mahsa; Larijani, Leila; Baikpour, Masoud; Khayamzadeh, Maryam

2016-01-01

Background Postoperative outcome of spinal meningiomas is an important issue in surgery decision-making. There are limited and conflicting data in the literature about the prognostic factors influencing recovery, especially about the histopathologic subtypes. Objectives This study was carried out to evaluate the effect of some of these factors on postoperative outcome. Patients and Methods This study was performed on 39 patients operated for spinal meningioma between October 1998 and January 2012; their histopathologic subtype was determined according to WHO criteria. The follow up period ranged between 8 - 120 months. The influence of histopathologic subtype, grade, age, sex, surgical approach, local adhesion and anatomical location was assessed according to Frankel classification of neurologic deficit. Results From a total number of 39 spinal meningiomas, 34 cases were WHO grade I, from which 15 cases were psammomatous, 7 cases were meningothelial, 9 cases were transitional and 3 cases were fibroblastic. Five cases were grade II, 3 of which had clear cell appearance and the remaining 2 had chordoid appearance. The mean age was 51.6 (22 to 76) years; 25 cases were female and 14 cases were male. This study revealed that grade II meningioma cases had poor prognosis in all 5 cases and psammomatous subtype had poor postoperative outcome in 40% of cases while the other subtypes had good outcome in all cases (P = 0.026). Cervical location of the tumor was also related with poor outcome in 37.5% of the cases, while 22.5% had poor outcome in other locations (P = 0.029). Age below and above 45 years and sex had no significant influence on the outcome. Conclusions Spinal meningiomas of psammomatous type and grade II spinal meningiomas are associated with less favorable postoperative neurologic outcome. Cervical location has also a negative correlation with a good outcome. PMID:27482326

Does Histologic Subtype Influence the Post-Operative Outcome in Spinal Meningioma?

PubMed

Zham, Hanieh; Moradi, Afshin; Rakhshan, Azadeh; Zali, Alireza; Rahbari, Ali; Raee, Mohammadreza; Ashrafi, Farzad; Ahadi, Mahsa; Larijani, Leila; Baikpour, Masoud; Khayamzadeh, Maryam

2016-04-01

Postoperative outcome of spinal meningiomas is an important issue in surgery decision-making. There are limited and conflicting data in the literature about the prognostic factors influencing recovery, especially about the histopathologic subtypes. This study was carried out to evaluate the effect of some of these factors on postoperative outcome. This study was performed on 39 patients operated for spinal meningioma between October 1998 and January 2012; their histopathologic subtype was determined according to WHO criteria. The follow up period ranged between 8 - 120 months. The influence of histopathologic subtype, grade, age, sex, surgical approach, local adhesion and anatomical location was assessed according to Frankel classification of neurologic deficit. From a total number of 39 spinal meningiomas, 34 cases were WHO grade I, from which 15 cases were psammomatous, 7 cases were meningothelial, 9 cases were transitional and 3 cases were fibroblastic. Five cases were grade II, 3 of which had clear cell appearance and the remaining 2 had chordoid appearance. The mean age was 51.6 (22 to 76) years; 25 cases were female and 14 cases were male. This study revealed that grade II meningioma cases had poor prognosis in all 5 cases and psammomatous subtype had poor postoperative outcome in 40% of cases while the other subtypes had good outcome in all cases (P = 0.026). Cervical location of the tumor was also related with poor outcome in 37.5% of the cases, while 22.5% had poor outcome in other locations (P = 0.029). Age below and above 45 years and sex had no significant influence on the outcome. Spinal meningiomas of psammomatous type and grade II spinal meningiomas are associated with less favorable postoperative neurologic outcome. Cervical location has also a negative correlation with a good outcome.

Frequent NF2 gene transcript mutations in sporadic meningiomas and vestibular schwannomas

DOE Office of Scientific and Technical Information (OSTI.GOV)

Deprez, R.H.L.; Groen, N.A.; Zwarthoff, E.C.

1994-06-01

The gene for the hereditary disorder neurofibromatosis type 2 (NF2), which predisposes for benign CNS tumors such as vestibular schwannomas and meningiomas, has been assigned to chromosome 22 and recently has been isolated. Mutations in the NF2 gene were found in both sporadic meningiomas and vestibular schwannomas. However, so far only 6 of the 16 exons of the gene have been analyzed. In order to extend the analysis of an involvement of the NF2 gene in the sporadic counterparts of these NF2-related tumors, the authors have used reverse transcriptase-PCR amplification followed by SSCP and DNA sequence analysis to screen formore » mutations in the coding region of the NF2 gene. Analysis of the NF2 gene transcript in 53 unrelated patients with meningiomas and vestibular schwannomas revealed mutations in 32% of the sporadic meningiomas (n = 44), in 50% of the sporadic vestibular schwannomas (n = 4), in 100% of the tumors found in NF2 patients (n = 2), and in one of three tumors from multiple-meningioma patients. Of the 18 tumors in which a mutation in the NF2 gene transcript was observed and the copy number of chromosome 22 could be established, 14 also showed loss of (parts of) chromosome 22. This suggests that in sporadic meningiomas and NF2-associated tumors the NF2 gene functions as a recessive tumor-suppressor gene. The mutations detected resulted mostly in frameshifts, predicting truncations starting within the N-terminal half of the putative protein. 23 refs., 2 figs. 3 tabs.« less

Morbidity and Mortality Associated With Meningioma After Cranial Radiotherapy: A Report From the Childhood Cancer Survivor Study

PubMed Central

Moskowitz, Chaya S.; Chou, Joanne F.; Mazewski, Claire M.; Neglia, Joseph P.; Armstrong, Gregory T.; Leisenring, Wendy M.; Robison, Leslie L.; Oeffinger, Kevin C.

2017-01-01

Purpose Little is known about neurologic morbidity attributable to cranial radiotherapy (CRT) –associated meningiomas. Materials and Methods From 4,221 survivors exposed to CRT in the Childhood Cancer Survivor Study, a diagnosis of meningioma and onset of neurologic sequelae were ascertained. Cox proportional hazards regression was used to estimate hazard ratios (HR) and 95% CIs to evaluate the factors associated with neurologic sequelae after subsequent meningioma. Results One hundred ninety-nine meningiomas were identified among 169 participants. The median interval from primary cancer to meningioma diagnosis was 22 years (5 to 37 years). The cumulative incidence of a subsequent meningioma by age 40 years was 5.6% (95% CI, 4.7% to 6.7%). CRT doses of 20 to 29.9 Gy (HR, 1.6; 95% CI,1.0 to 2.6) and doses ≥ 30 Gy (HR, 2.6; 95% CI, 1.6 to 4.2) were associated with an increased risk of meningioma compared with CRT doses of 1.5 to 19.9 Gy (P < .001). Within 6 months before or subsequent to a meningioma diagnosis, 20% (30 of 149) reported at least one new neurologic sequela, including seizures (8.3%), auditory-vestibular-visual deficits (6%), focal neurologic dysfunction (7.1%), and severe headaches (5.3%). Survivors reporting a meningioma had increased risks of neurologic sequelae > 5 years after primary cancer diagnosis, including seizures (HR, 10.0; 95% CI, 7.0 to 15.3); auditory-vestibular-visual sensory deficits (HR, 2.3; 95% CI, 1.3 to 4.0); focal neurologic dysfunction (HR, 4.9; 95% CI, 3.2 to 7.5); and severe headaches (HR, 3.2; 95% CI, 1.9 to 5.4). With a median follow-up of 72 months after meningioma diagnosis (range, 3.8 to 395 months), 22 participants (13%) were deceased, including six deaths attributed to a meningioma. Conclusion Childhood cancer survivors exposed to CRT and subsequently diagnosed with a meningioma experience significant neurologic morbidity. PMID:28339329

Quantitative evaluation of benign meningioma and hemangiopericytoma with peritumoral brain edema by 64-slice CT perfusion imaging.

PubMed

Ren, Guang; Chen, Shuang; Wang, Yin; Zhu, Rui-jiang; Geng, Dao-ying; Feng, Xiao-yuan

2010-08-05

Hemangiopericytomas (HPCs) have a relentless tendency for local recurrence and metastases, differentiating between benign meningiomas and HPCs before surgery is important for both treatment planning and the prognosis appraisal. The purpose of this study was to evaluate the correlations between CT perfusion parameters and microvessel density (MVD) in extra-axial tumors and the possible role of CT perfusion imaging in preoperatively differentiating benign meningiomas and HPCs. Seventeen patients with benign meningiomas and peritumoral edema, 12 patients with HPCs and peritumoral edema underwent 64-slice CT perfusion imaging pre-operation. Perfusion was calculated using the Patlak method. The quantitative parameters, include cerebral blood volume (CBV), permeability surface (PS) of parenchyma, peritumoral edema among benign meningiomas and HPCs were compared respectively. CBV and PS in parenchyma, peritumoral edema of benign meningiomas and HPCs were also compared to that of the contrallateral normal white matter respectively. The correlations between CBV, PS of tumoral parenchyma and MVD were examined. The value of CBV and PS in parenchyma of HPCs were significantly higher than that of benign meningiomas (P < 0.05), while the values of CBV and PS in peritumoral edema of benign meningiomas and HPCs were not significantly different (P > 0.05). MVD in parenchyma of HPCs were significantly higher than that of benign meningiomas (P < 0.05). There were positive correlations between CBV and MVD (r = 0.648, P < 0.05), PS and MVD (r = 0.541, P < 0.05) respectively. Furthermore, the value of CBV and PS in parenchyma of benign meningiomas and HPCs were significantly higher than that of contrallateral normal white matter (P < 0.05), the value of CBV in peritumoral edema of benign meningiomas and HPCs were significantly lower than that of contrallateral normal white matter (P < 0.05), while the value of PS in peritumoral edema of benign meningiomas and HPCs were not significantly

Microcystic Variant of an Intraosseous Meningioma in the Frontal Area: A Case Report

PubMed Central

2014-01-01

Meningiomas located inside the bone of the calvaria belong to the group of rare types of tumours. The microcystic variant is the least common in this area. Due to their similarity to other tumours in this area, the imaging test of those tumours may constitute the source of an improper preoperative diagnosis. According to the records of the Department of Neurosurgery in Bielsko-Biała, 133 patients diagnosed with an intracranial meningioma confirmed by a histopathological test were operated in the last 10 years (2004–2014). In the histopathological test, three patients were diagnosed with the microcystic variant, which constitutes 2.25% of the cases. Only one variant of microcystic meningioma was located inside the bone, which constitutes 0.75% of all the meningiomas operated. PMID:25031877

Alternative Splicing of CHEK2 and Codeletion with NF2 Promote Chromosomal Instability in Meningioma1

PubMed Central

Yang, Hong Wei; Kim, Tae-Min; Song, Sydney S; Shrinath, Nihal; Park, Richard; Kalamarides, Michel; Park, Peter J; Black, Peter M; Carroll, Rona S; Johnson, Mark D

2012-01-01

Mutations of the NF2 gene on chromosome 22q are thought to initiate tumorigenesis in nearly 50% of meningiomas, and 22q deletion is the earliest and most frequent large-scale chromosomal abnormality observed in these tumors. In aggressive meningiomas, 22q deletions are generally accompanied by the presence of large-scale segmental abnormalities involving other chromosomes, but the reasons for this association are unknown. We find that large-scale chromosomal alterations accumulate during meningioma progression primarily in tumors harboring 22q deletions, suggesting 22q-associated chromosomal instability. Here we show frequent codeletion of the DNA repair and tumor suppressor gene, CHEK2, in combination with NF2 on chromosome 22q in a majority of aggressive meningiomas. In addition, tumor-specific splicing of CHEK2 in meningioma leads to decreased functional Chk2 protein expression. We show that enforced Chk2 knockdown in meningioma cells decreases DNA repair. Furthermore, Chk2 depletion increases centrosome amplification, thereby promoting chromosomal instability. Taken together, these data indicate that alternative splicing and frequent codeletion of CHEK2 and NF2 contribute to the genomic instability and associated development of aggressive biologic behavior in meningiomas. PMID:22355270

Expanded Endoscopic Endonasal Approaches to Skull Base Meningiomas

PubMed Central

Prosser, J. Drew; Vender, John R.; Alleyne, Cargill H.; Solares, C. Arturo

2012-01-01

Anterior cranial base meningiomas have traditionally been addressed via frontal or frontolateral approaches. However, with the advances in endoscopic endonasal treatment of pituitary lesions, the transphenoidal approach is being expanded to address lesions of the petrous ridge, anterior clinoid, clivus, sella, parasellar region, tuberculum, planum, olfactory groove, and crista galli regions. The expanded endoscopic endonasal approach (EEEA) has the advantage of limiting brain retraction and resultant brain edema, as well as minimizing manipulation of neural structures. Herein, we describe the techniques of transclival, transphenoidal, transplanum, and transcribiform resections of anterior skull base meningiomas. Selected cases are presented. PMID:23730542

Olfactory groove meningiomas.

PubMed

Hentschel, Stephen J; DeMonte, Franco

2003-06-15

Olfactory groove meningiomas (OGMs) arise over the cribriform plate and may reach very large sizes prior to presentation. They can be differentiated from tuberculum sellae meningiomas because OGMs arise more anterior in the skull base and displace the optic nerve and chiasm inferiorly rather than superiorly. The authors searched the neurosurgery database at the M. D. Anderson Cancer Center for cases of OGM treated between 1993 and 2003. The records of these patients were then reviewed retrospectively for details regarding clinical presentation, imaging findings, surgical results and complications, and follow-up status. Thirteen patients, (12 women and one man, mean age 56 years) harbored OGMs (mean size 5.7 cm). All patients underwent bifrontal craniotomies and biorbital osteotomies. There were 11 complete resections (including the hyperostotic bone and dura of the cribriform plate and any extension into the ethmoid sinuses) and two subtotal resections with minimal residual tumor left in patients with recurrent lesions. No complication directly due to the surgery occurred in any patient. There were no recurrences in a mean follow-up period of 2 years (range 0-5 years). With current microsurgical techniques, the results of OGM resection are excellent, with a high rate of total resection and a low incidence of complications. All hyperostotic bone should be removed with the dura of the anterior skull base to minimize the risk of recurrence.

Cellular phones, cordless phones, and the risks of glioma and meningioma (Interphone Study Group, Germany).

PubMed

Schüz, Joachim; Böhler, Eva; Berg, Gabriele; Schlehofer, Brigitte; Hettinger, Iris; Schlaefer, Klaus; Wahrendorf, Jürgen; Kunna-Grass, Katharina; Blettner, Maria

2006-03-15

The widespread use of cellular telephones has generated concern about possible adverse health effects, particularly brain tumors. In this population-based case-control study carried out in three regions of Germany, all incident cases of glioma and meningioma among patients aged 30-69 years were ascertained during 2000-2003. Controls matched on age, gender, and region were randomly drawn from population registries. In total, 366 glioma cases, 381 meningioma cases, and 1,494 controls were interviewed. Overall use of a cellular phone was not associated with brain tumor risk; the respective odds ratios were 0.98 (95% confidence interval (CI): 0.74, 1.29) for glioma and 0.84 (95% CI: 0.62, 1.13) for meningioma. Among persons who had used cellular phones for 10 or more years, increased risk was found for glioma (odds ratio = 2.20, 95% CI: 0.94, 5.11) but not for meningioma (odds ratio = 1.09, 95% CI: 0.35, 3.37). No excess of temporal glioma (p = 0.41) or meningioma (p = 0.43) was observed in cellular phone users as compared with nonusers. Cordless phone use was not related to either glioma risk or meningioma risk. In conclusion, no overall increased risk of glioma or meningioma was observed among these cellular phone users; however, for long-term cellular phone users, results need to be confirmed before firm conclusions can be drawn.

Hitting a moving target: evolution of a treatment paradigm for atypical meningiomas amid changing diagnostic criteria.

PubMed

Pearson, Blake E; Markert, James M; Fisher, Winfield S; Guthrie, Barton L; Fiveash, John B; Palmer, Cheryl A; Riley, Kristen

2008-01-01

The World Health Organization (WHO) reclassified atypical meningiomas in 2000, creating a more clear and broadly accepted definition. In this paper, the authors evaluated the pathological and clinical transition period for atypical meningiomas according to the implementation of the new WHO grading system at their institution. A total of 471 meningiomas occurring in 440 patients between 1994 and 2006 were retrospectively reviewed to determine changes in diagnostic rates, postoperative treatment trends, and early outcomes. Between 1994 and 2000, the incidence of the atypical meningiomas ranged from 0 to 3/year, or 4.4% of the meningiomas detected during the entire period. After 2002, the annual percentage of atypical meningiomas rose over a 2-year period, leveling off at between 32.7 and 35.5% between 2004 and 2006. The authors also found a recent trend toward increased use of adjuvant radiation therapy for incompletely resected atypical meningiomas. Prior to 2003, 18.7% were treated with this therapy; after 2003, 34.4% of lesions received this treatment. Incompletely resected tumors were treated with some form of radiation 76% of the time. In cases of complete resection, most patients were not given adjuvant therapy but were expectantly managed by close monitoring using serial imaging and by receiving immediate treatment for tumor recurrence. The overall recurrence rate for expectantly managed tumors was 9% over 28.2 months, and 75% of recurrences responded to delayed radiation therapy. The authors documented a significant change in the proportion of meningiomas designated as atypical during a transition period from 2002 to 2004, and propose a conservative strategy for the use of radiation therapy in atypical meningiomas.

Long-term follow-up of surgical resection of microcystic meningiomas.

PubMed

Kalani, M Yashar S; Cavallo, Claudio; Coons, Stephen W; Lettieri, Salvatore C; Nakaji, Peter; Porter, Randall W; Spetzler, Robert F; Feiz-Erfan, Iman

2015-04-01

Microcystic meningioma is a rare tumor with myxoid and microcystic features. Our objective was to evaluate the efficacy of surgical resection of microcystic meningioma. Between December 1985 and October 2000 we treated 25 microcystic meningioma patients with surgical resection. We retrospectively analyzed the results including the long-term follow-up of this patient population. We identified 15 women and 10 men with a mean age of 53.8 years (24-76 years) who had microcystic meningiomas treated with surgery. Based on the Simpson grade, we found four Grade I (16%), 16 Grade II (64%), three Grade III (12%) and two Grade IV (8%) resections. The mean preoperative Karnofsky Performance Scale (KPS) score was 80.3 (range 60-100). The mean postoperative KPS score was 90.4 (range 60-100). At a mean follow-up of 101.7 months (range 16-221) the KPS score improved to a mean of 93.8. The recurrence/progression free survival (RFS/PFS) rates at 3 and 5 years were 96% and 88%, respectively. The 3 and 5 year RFS/PFS rates based on the Simpson grade were evaluated. The 3 year RFS/PFS rates for Grade I, II, III and IV were 100%, 100%, 66.6% and 100%, respectively. The 5 year RFS/PFS rates were 66.6%, 90%, 66.6% and 100%, respectively. Microcystic meningioma is a rare tumor, which is characterized by extracellular microcystic spaces filled by edematous fluid and peritumoral edema. Following surgical resection these tumors have a positive prognosis with a benign course. The surgical outcomes seem to be associated with the risks related to the surgical procedure. Copyright © 2015 Elsevier Ltd. All rights reserved.

[Constitutional syndrome as a presentation of a cerebellopontine meningioma].

PubMed

Ruiz-Serrato, A; Mata-Palma, A; Olmedo-Llanes, J; García-Ordóñez, M A

2014-03-01

Meningiomas are basically benign tumours arising in the meninges and account for 15-25% of intracranial tumours in adults. It is clinically signs are due to compression of the neighbouring structures, with the main symptoms being migraine, behavioural changes, and neurological deficits. We present a case where constitutional syndrome was the first and principal manifestation of an intracranial cerebellopontine meningioma. Copyright © 2012 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España. All rights reserved.

[Hydrocephalus Associated with Small Clinoidal Meningioma that Resolved after Tumor Removal:A Case Report].

PubMed

Fujiwara, Hidemoto; Aiba, Toyotaka; Watanabe, Toru; Hiraishi, Tetsuya; Fujii, Yukihiko

2016-12-01

Small meningiomas causing hydrocephalus without obstruction of the ventricular system are rare. Herein, we report a case of small clinoidal meningioma with communicating hydrocephalus, which resolved after tumor removal. A 70-year-old woman presented with a 1-month history of memory disturbance followed by gait disturbance. MR images revealed a right clinoidal meningioma, 2 cm in diameter, and dilatation of the ventricles suggesting communicating hydrocephalus. The cerebrospinal fluid(CSF)pressure was 130 mmH₂O, as determined via a lumbar puncture. High concentrations of protein(65mg/dL)were detected in the lumbar CSF. The tumor was completely removed via a frontotemporal craniotomy. Higher protein concentrations(94mg/dL)were detected in the CSF obtained intraoperatively from the sylvian cistern. The histopathological diagnosis was meningothelial meningioma. The patient's symptoms improved markedly after surgery. Postoperative MR images revealed resolution of the hydrocephalus. The lumbar CSF protein concentration returned to normal(43mg/dL). Neither tumor recurrence nor progression of hydrocephalus has been observed for 4 years. Communicating hydrocephalus, associated with a small meningioma at the supratentorial region, has not been described. Previous studies have shown that patients with meningioma may develop communicating hydrocephalus after tumor removal or stereotactic radiosurgery. Thus, it is interesting that the small supratentorial meningioma in our case developed communicating hydrocephalus without any therapeutic intervention. Considering the CSF protein concentration, we speculate that the hydrocephalus was the result of CSF malabsorption associated with high CSF protein concentration and CSF pathway obstruction at the suprasellar cistern caused by the tumor.

Expression of p40 (∆Np63) protein in meningiomas, an unexpected finding: immunohistochemical study and evaluation of its possible prognostic role.

PubMed

Guadagno, Elia; Del Basso De Caro, Marialaura; Pignatiello, Sara; Sciammarella, Concetta; Solari, Domenico; Cappabianca, Paolo; Maiuri, Francesco; Dones, Flavia

2016-09-01

According to the 2007 WHO (World Health Organization) Classification, meningiomas are divided into three grades of malignancy, with different recurrence rate, based exclusively on histopathological parameters. Loss/reduction of PgR (Progesterone Receptor) expression and increased Ki67 L.I. (Labeling Index) have been proven as possible prognostic factors able to predict the relapse of the disease. However, they sometimes result unreliable, especially when discordant. p40 is the short form of the p53 homologue gene p63, also named ∆Np63, and its antibody has recently been introduced as a highly specific diagnostic marker of the squamous cell carcinoma of the lung. Nevertheless its expression has been found in many other unconventional sites (e.g. placenta, urotheluim, etc). Herein we assessed the immuno-expression of p40 protein in a series of 72 meningiomas (35 grade I and 37 grade II) and analyzed its correlation with clinicopathological parameters, overall survival and recurrence free interval. We found that a high p40 score correlated with high histological grade, presence of recurrence, increased Ki67 L.I. and loss/reduction of PgR signal. Moreover, a higher expression of p40 was shown to be a significant prognostic factor for the development of recurrences and resulted a prognostic independent variable in multivariate analysis. Overall, for the first time, we investigated the expression of p40 protein in meningiomas and explored its usefulness as prognostic marker in addition to PgR and Ki67 L.I.

Unususpected meningioma in a patient with pituitary gigantism. Case report with autopsy findings.

PubMed

Stock, J M; Ghatak, N R; Oppenheimer, J H

1975-06-01

A unique example of a clinically unsuspected large parasellar meningioma is described in a 36-yr-old pituitary giant who had been treated initially with conventional irradiation, subsequently by surgical excision of an acidophil adenoma, and ultimately with medroxyprogesterone acetate (MPA) prior to his demise. The patient died of increased intracranial pressure resulting from a combined mass effect of the meningioma and recurrent tumor. The relationship between radiation and the development of the meningioma is discussed, as well as the fine ultrastructure of a highly functioning acidophil adenoma.

Castleman's disease associated with a cerebellar chordoid meningioma and intestinal lymphangiectasia.

PubMed

Jeon, Chul Jin; Kim, Mi Jin; Lee, Jong Seung; Lee, Ji Hyuk; Kong, Doo-Sik; Shin, Hyung Jin; Suh, Yeon Lim; Kim, Kyoung Mee; Choe, Yon Ho

2010-11-01

Castleman's disease (CD) is a rare nonneoplastic lymphoproliferative disorder of unknown etiology. It is characterized by enlarged hyperplastic lymph nodes, usually presenting as a localized mass. Although an intracranial location is very uncommon, it should be considered in the differential diagnosis of a chordoid meningioma. We describe a pediatric case of CD with a cerebellar chordoid meningioma and intestinal lymphangiectasia.

Canine orbital meningiomas: a review of 22 cases.

PubMed

Mauldin, E.A.; Deehr, A.J.; Hertzke, D.; Dubielzig, R.R.

2000-01-01

Clinical and pathologic features of primary orbital meningiomas in the dog were reviewed. Twenty-two meningiomas, confined to the orbit, were identified from the Comparative Ophthalmic Pathology Laboratory of Wisconsin from 1981 to 1997. The dogs ranged in age from 3 to 17 years (mean = 9.2 years). The clinical presentation, reported in 20 cases, was indicative of a retrobulbar mass and included exophthalmos and orbital swelling (18/20), and papilledema or abnormalities of the posterior segment (7/20). Visual acuity was reported in 15 cases; of those, 12 dogs were blind in the affected eye. Follow-up information was obtained on 17 cases; six dogs developed local recurrence of the neoplasm. Two dogs with recurrent neoplasms simultaneously developed blindness in the opposite eye. Extension along the optic nerve to the optic chiasm was suspected. No metastasis was found at the time of the study. Enucleation with excisional biopsy was effective therapy to date in 11 cases (0.2-4.5 years follow-up time). All neoplasms were located within the vicinity of the optic nerve and, when sectioned through the optic nerve head, appeared to completely envelope the nerve. The neoplastic cells were arranged in tight whorls and bundles characteristic of meningiomas. Most tumors had islands of chondroid and osseous metaplasia (17/22). Ocular invasion was limited to small foci in the posterior choroid or optic nerve head of six dogs. Immunoperoxidase stains on 10 cases were positive for vimentin and S-100, but negative for cytokeratin. Electron microscopy revealed complex interdigitations between cell membranes and few desmosomal intercellular attachments. Primary orbital meningiomas have a characteristic histologic appearance and may recur locally after surgical excision.

Meningioma Causing Visual Impairment: Outcomes and Toxicity After Intensity Modulated Radiation Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Maclean, Jillian, E-mail: jillian.maclean@uclh.nhs.uk; Fersht, Naomi; Bremner, Fion

2013-03-15

Purpose: To evaluate ophthalmologic outcomes and toxicity of intensity modulated radiation therapy (IMRT) in patients with meningiomas causing visual deficits. Methods and Materials: A prospective observational study with formal ophthalmologic and clinical assessment of 30 consecutive cases of meningioma affecting vision treated with IMRT from 2007 to 2011. Prescriptions were 50.4 Gy to mean target dose in 28 daily fractions. The median follow-up time was 28 months. Twenty-six meningiomas affected the anterior visual pathway (including 3 optic nerve sheath meningiomas); 4 were posterior to the chiasm. Results: Vision improved objectively in 12 patients (40%). Improvements were in visual field (5/16more » patients), color vision (4/9 patients), acuity (1/15 patients), extraocular movements (3/11 patients), ptosis (1/5 patients), and proptosis (2/6 patients). No predictors of clinical response were found. Two patients had minor reductions in tumor dimensions on magnetic resonance imaging, 1 patient had radiological progression, and the other patients were stable. One patient experienced grade 2 keratitis, 1 patient had a minor visual field loss, and 5 patients had grade 1 dry eye. Conclusion: IMRT is an effective method for treating meningiomas causing ophthalmologic deficits, and toxicity is minimal. Thorough ophthalmologic assessment is important because clinical responses often occur in the absence of radiological change.« less

Selective intraarterial gene delivery into a canine meningioma.

PubMed

Chauvet, A E; Kesava, P P; Goh, C S; Badie, B

1998-05-01

The goal of this study was to evaluate gene delivery to a benign brain tumor. A recombinant adenovirus vector bearing the Escherichia coli beta-galactosidase reporter gene was selectively injected into the vascular supply of a spontaneously occurring canine olfactory groove meningioma. The tumor and a small amount of peritumoral brain tissue were removed 5 days after viral injection and stained with X-Gal to assess gene delivery. The authors noted significant beta-galactosidase gene expression by the tumor, but not by surrounding brain tissue. No obvious viral-related cytotoxicity was noted. The authors found that meningiomas can be successfully transduced by adenovirus vectors by using endovascular techniques.

HCG variants, the growth factors which drive human malignancies

PubMed Central

Cole, Laurence A

2012-01-01

The term human chorionic gonadotropin (hCG) refers to a group of 5 molecules, each sharing the common amino acid sequence but each differing in meric structure and carbohydrate side chain structure. The 5 molecules are each produced by separate cells and each having separate biological functions. hCG and sulfated hCG are hormones produced by placental syncytiotrophoblast cells and pituitary gonadotrope cells. Hyperglycosylated hCG is an autocrine produced by placental cytotrophoblast cells. Hyperglycosylated hCG drives malignancy in placental cancers, and in testicular and ovarian germ cell malignancies. hCGβ and hyperglycosylated hCGβ are autocrines produce by most advanced malignancies. These molecules, particularly the malignancy promoters are presented in this review on hCG and cancer. hCGβ and hyperglycosylated hCGβ are critical to the growth and invasion, or malignancy of most advanced cancers. In many ways, while hCG may appear like a nothing, a hormone associated with pregnancy, it is not, and may be at the center of cancer research. PMID:22206043

Balloon-assisted embolization of skull base meningioma with liquid embolic agent.

PubMed

Abdel Kerim, Amr; Bonneville, Fabrice; Jean, Betty; Cornu, Philippe; LeJean, Lise; Chiras, Jacques

2010-01-01

The authors report a novel technique of balloon-assisted embolization of a skull base meningioma supplied by a branch of the cavernous segment of the internal carotid artery using liquid embolic agent. A temporarily inflated balloon distal to the meningioma's feeding vessel may improve the access to this small branch and may reduce the chances of unintended reflux during delivery of the liquid embolic agent.

Body mass index, physical activity, and risk of adult meningioma and glioma: A meta-analysis.

PubMed

Niedermaier, Tobias; Behrens, Gundula; Schmid, Daniela; Schlecht, Inga; Fischer, Beate; Leitzmann, Michael F

2015-10-13

Whether adiposity and lack of physical activity affect the risk for developing meningioma and glioma is poorly understood. Our objective was to characterize these associations in detail. We conducted a systematic review and meta-analysis of adiposity and physical activity in relation to meningioma and glioma using cohort and case-control studies published through February 2015. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We identified 12 eligible studies of body mass index (BMI) and 6 studies of physical activity, comprising up to 2,982 meningioma cases and 3,057 glioma cases. Using normal weight as the reference group, overweight (summary relative risk [RR] = 1.21, 95% confidence interval [CI] = 1.01-1.43) and obesity (RR = 1.54, 95% CI = 1.32-1.79) were associated with increased risk of meningioma. In contrast, overweight (RR = 1.06, 95% CI = 0.94-1.20) and obesity (RR = 1.11, 95% CI = 0.98-1.27) were unrelated to glioma. Similarly, dose-response meta-analyses revealed a statistically significant positive association of BMI with meningioma, but not glioma. High vs low physical activity levels showed a modest inverse relation to meningioma (RR = 0.73, 95% CI = 0.61-0.88) and a weak inverse association with glioma (RR = 0.86, 95% CI = 0.76-0.97). Relations persisted when the data were restricted to prospective studies, except for the association between physical activity and glioma, which was rendered statistically nonsignificant (RR = 0.91, 95% CI = 0.77-1.07). Adiposity is related to enhanced risk for meningioma but is unassociated with risk for glioma. Based on a limited body of evidence, physical activity is related to decreased risk of meningioma but shows little association with risk of glioma. © 2015 American Academy of Neurology.

Fidelity of DNA Replication in Normal and Malignant Human Breast Cells

DTIC Science & Technology

1998-07-01

synthesome has been extensively demonstrated to carry out full length DNA replication in vitro, and to accurately depict the DNA replication process as it...occurs in the intact cell. By examining the fidelity of the DNA replication process carried out by the DNA synthesome from a number of breast cell types...we have demonstrated for the first time, that the cellular DNA replication machinery of malignant human breast cells is significantly more error-prone than that of non- malignant human breast cells.

Is Psychiatric Depression a Presenting Neurologic Sign of Meningioma? A Critical Review of the Literature with Causative Etiology.

PubMed

Kessler, Remi A; Loewenstern, Joshua; Kohli, Karan; Shrivastava, Raj K

2018-04-01

Benign meningiomas constitute 80%-90% of all meningiomas and represent the most common type of central nervous system tumor in adults. The vast majority of meningiomas are minimally symptomatic or asymptomatic early in their onset and thereby can often result in delayed diagnosis. Early diagnosis of meningioma is critical, as it can maximize treatment options and improve outcomes and survival. Although seizures and focal neurologic deficits are considered to be the most prevalent symptoms, depression also may be an important and significant sign. A subtle neurologic depression may be an even early presenting sign of meningioma and may precede more traditional presenting symptoms. We performed a comprehensive literature review that analyzes the results of prospective studies and case reports on this topic. Our findings show evidence to suggest that depression may be correlated with meningioma presentation. Its prevalence is possibly increased with an anterior location of the tumor. For patients who exhibit nuances of depression without a history of psychiatric illness, an index of suspicion for meningioma may be warranted. Copyright © 2018 Elsevier Inc. All rights reserved.

Long noncoding RNA LINC00460 targets miR-539/MMP-9 to promote meningioma progression and metastasis.

PubMed

Xing, Hongshun; Wang, Shilei; Li, Quancai; Ma, Yongqian; Sun, Peng

2018-06-12

Emerging evidence reveal that long noncoding RNAs (lncRNAs) participates in the epigenetic regulation of pathophysiological process. However, the deepgoing role of lncRNAs on meningioma is still unclear. In present study, we investigate the roles of lncRNA LINC00460 in meningeoma tissue and uncover its molecular mechanism. Results revealed that LINC00460 expression level was significantly up-regulated in meningeoma tissues and malignant meningeoma cell lines (IOMM-Lee, CH157-MN). Mechanically, loss-of-function assays showed that LINC00460 knockdown significantly suppressed the proliferation ability, increased the apoptosis and decreased the proteins (MMP-2, MMP-9, ZEB1) expression. Bioinformatics tools predicted that miR-539 both targeted with the 3'-UTR of LINC00460 and MMP-9 mRNA, which was confirmed by luciferase reporter assay and western blot analysis. In summary, our study reveals that LINC00460 promotes MMP-9 expression through targeting miR-539, acting as an oncogenic RNA in the meningeoma malignancy and accelerating the proliferation and metastasis of meningeoma. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Reduced GNG2 expression levels in mouse malignant melanomas and human melanoma cell lines

PubMed Central

Yajima, Ichiro; Kumasaka, Mayuko Y; Naito, Yuji; Yoshikawa, Toshikazu; Takahashi, Hiro; Funasaka, Yoko; Suzuki, Tamio; Kato, Masashi

2012-01-01

Heterotrimeric G protein is composed of a Gα-subunit and a Gβγ-dimer. Previous studies have revealed that Gβγ-dimers including the Gγ2 subunit (Gng2/GNG2) are associated with cell proliferation, differentiation, invasion and angiogenesis. At present, however, there is no information on the expression level of Gng2/GNG2 alone in any kind of tumor. In this study, we performed DNA microarray analysis in a benign melanocytic tumor and a malignant melanoma from RET-transgenic mice (RET-mice). Gng2 transcript expression levels in a malignant melanoma were less than 1/10 of the level in a benign tumor. The difference in Gng2 transcript expression levels between benign tumors and malignant melanomas was greatest among all of the G protein γ subunits examined in this study. Moreover, protein expression levels of Gng2 were decreased in malignant melanomas compared with those in benign melanocytic tumors in RET-mice. Analysis of human malignant melanomas also showed reduced GNG2 protein expression levels in five human malignant melanoma cell lines compared with the expression levels in normal human epithelial melanocytes (NHEM). Thus, we demonstrated for the first time that Gng2/GNG2 expression levels are reduced in malignant melanoma, suggesting that GNG2 could be a novel biomarker for malignant melanoma. PMID:22679562

Skull Base Meningiomas and Cranial Nerves Contrast Using Sodium Fluorescein: A New Application of an Old Tool

PubMed Central

da Silva, Carlos Eduardo; da Silva, Vinicius Duval; da Silva, Jefferson Luis Braga

2014-01-01

Objective The identification of cranial nerves is one of the most challenging goals in the dissection of skull base meningiomas. The authors present an application of sodium fluorescein (SF) in skull base meningiomas with the purpose of improving the identification of cranial nerves. Design A prospective study within-subjects design. Setting Hospital Ernesto Dornelles, Porto Alegre, Brazil. Participants Patients with skull base meningiomas. Main Outcomes Measures Cranial nerve identification. Results The group of nine meningiomas was composed of one cavernous sinus, three petroclival, one tuberculum sellae, two sphenoid wing, one olfactory groove, and one temporal floor meningioma. The SF enhancement in all tumors was strong, and the contrast with cranial nerves clearly evident. There were one definite olfactory nerve deficit, one transient abducens deficit, and one definite hemiparesis. All lesions were resected (Simpson grades 1 and 2). The analysis of the difference of the delta SF wavelength between the meningiomas and cranial nerve contrast was performed by the Wilcoxon signed rank test and showed p = 0.011. Conclusions The contrast between the enhanced meningiomas and cranial nerves was evident and assisted in the visualization and microsurgical dissection of these structures. The anatomical preservation of these structures was improved using the contrast. PMID:27054056

Skull Base Meningiomas and Cranial Nerves Contrast Using Sodium Fluorescein: A New Application of an Old Tool.

PubMed

da Silva, Carlos Eduardo; da Silva, Vinicius Duval; da Silva, Jefferson Luis Braga

2014-08-01

Objective The identification of cranial nerves is one of the most challenging goals in the dissection of skull base meningiomas. The authors present an application of sodium fluorescein (SF) in skull base meningiomas with the purpose of improving the identification of cranial nerves. Design A prospective study within-subjects design. Setting Hospital Ernesto Dornelles, Porto Alegre, Brazil. Participants Patients with skull base meningiomas. Main Outcomes Measures Cranial nerve identification. Results The group of nine meningiomas was composed of one cavernous sinus, three petroclival, one tuberculum sellae, two sphenoid wing, one olfactory groove, and one temporal floor meningioma. The SF enhancement in all tumors was strong, and the contrast with cranial nerves clearly evident. There were one definite olfactory nerve deficit, one transient abducens deficit, and one definite hemiparesis. All lesions were resected (Simpson grades 1 and 2). The analysis of the difference of the delta SF wavelength between the meningiomas and cranial nerve contrast was performed by the Wilcoxon signed rank test and showed p = 0.011. Conclusions The contrast between the enhanced meningiomas and cranial nerves was evident and assisted in the visualization and microsurgical dissection of these structures. The anatomical preservation of these structures was improved using the contrast.

Clear-Cell Meningioma: CT and MR Imaging Findings in Two Cases Involving the Spinal Canal and Cerebellopontine Angle

PubMed Central

Yu, Ki Bong; Kim, Hyung Jin; Suh, Chang Hae; Park, Hyung Chun; Kim, Eun Young; Han, Hye Seung

2002-01-01

Clear-cell meningioma is a rare subtype of meningioma which occurs at a younger age and has a higher recurrence rate than other subtypes. We report two cases of clear-cell meningioma, one in the thoracolumbar spinal canal and the other in the cerebellopontine angle. Though the CT and MR imaging findings were not different from those of ordinary meningioma, after surgical removal the condition recurred repeatedly in the patient with spinal canal involvement. PMID:12087202

Long-term chemotherapy with lomustine of intracranial meningioma occurring in a miniature schnauzer.

PubMed

Jung, Dong-In; Kim, Ha-Jung; Park, Chul; Kim, Ju-Won; Kang, Byeong-Teck; Lim, Chae-Young; Park, Eun-Hee; Sur, Jung-Hyang; Seo, Min-Ho; Hahm, Dae-Hyun; Park, Hee-Myung

2006-04-01

A 14-year-old male miniature schnauzer was referred to us because it was circling to the right. A mass in the diencephalon was noted on brain magnetic resonance images. The dura was thickened with marked linear enhancement after contrast administration. Based on diagnostic image analysis, this lesion strongly suggested meningioma. The patient's symptoms were well controlled by a combination therapy of prednisolone and lomustine (CCNU), and survived for thirteen months after diagnosis. This case was diagnosed as a meningioma based on histopathological findings. This report describes the clinical findings, imaging characteristics, and pathologic features of a diencephalic and mesencephalic meningioma and long-term survival after lomustine and prednisolone therapy.

Evaluation of ascitic soluble human leukocyte antigen-G for distinguishing malignant ascites from benign ascites.

PubMed

Sun, Juan; Chang, Yan-Xiang; Niu, Chun-Yan

2017-11-01

The overexpression of soluble human leukocyte antigen-G is associated with malignant tumours. The purpose of our study was to detect soluble human leukocyte antigen-G concentrations in ascites and to evaluate the value of ascitic soluble human leukocyte antigen-G for the diagnosis of malignant ascites. Enzyme-linked immunosorbent assay was used to detect soluble human leukocyte antigen-G levels in 64 patients with malignant ascites and 30 patients with benign ascites. Receiver operating characteristic curves were used to evaluate the diagnostic efficacy of ascitic soluble human leukocyte antigen-G for the detection of malignant ascites. Ascitic soluble human leukocyte antigen-G levels were significantly higher in the malignant ascites group than in the benign ascites group (20.718 ± 3.215 versus 12.467 ± 3.678 µg/L, t = 7.425, p < 0.001). The area under the receiver operating characteristic curve for ascitic soluble human leukocyte antigen-G was 0.957 (95% confidence interval, 0.872-0.992). At a cut-off value of 19.60 µg/L, the sensitivity and specificity of ascitic soluble human leukocyte antigen-G were 87.5% (95% confidence interval, 71.0%-96.5%) and 100% (95% confidence interval, 88.4%-100%), respectively. With respect to area under the receiver operating characteristic curve, sensitivity and specificity, ascitic carcinoembryonic antigen (0.810, 68.75% and 83.33%, respectively) and carbohydrate antigen 19-9 (0.710, 65.63% and 70%, respectively) significantly differed (all p < 0.05). In malignant ascites that were cytology-negative and biopsy-positive, the rate of positivity for ascitic soluble human leukocyte antigen-G was 75%, which was higher than the corresponding rates for ascitic carcinoembryonic antigen (31.25%) and carbohydrate antigen 19-9 (6.25%; both p < 0.05). In conclusion, The detection of ascitic soluble human leukocyte antigen-G exhibited good performance for diagnosing malignant ascites, and particularly those that

Ossified Intracranial Meningiomas: Description of the First Series of Cases and Review of the Literature.

PubMed

Caffo, Maria; Caruso, Gerardo; Barresi, Valeria; Tomasello, Francesco

2016-10-01

Metaplastic meningiomas are characterized by mesenchymal differentiation with formation of bone, cartilage, fat, or xanthomatous elements. However the presence of extensive areas of ossification is rare in meningiomas. In addition, intracranial location of ossified meningiomas is uncommon. Surgical management represents the optimal treatment for ossified meningiomas, but ossification may interfere with surgery and condition outcome. By reviewing patient records and contacting patients, families, and referring physicians, the following information was gathered: age, sex, tumor location, clinical presentation, preoperative and postoperative functional status, and surgical data. Each surgical specimen had been formalin-fixed, paraffin-embedded, and cut into parallel 4-μm-thick sections for histological evaluation. Our literature search identified 8 cases, all of whom had undergone surgical treatment. Histopathological analysis revealed the presence of disorganized bone spicules with solitary oval osteocytic nuclei and lined by osteoblasts, with clear evidence of bone tissue in at least 50% of tumor tissue. Here we present the largest series, to our knowledge, of surgically treated intracranial ossified meningiomas reported to date. The mechanism of ossification in these meningiomas remains unclear, and various hypotheses have been formulated. Complete lesion removal, or subtotal debulking in those cases characterized by tenacious adherences to vascular structures and/or critical areas, may represent the optimal treatment. Copyright © 2016 Elsevier Inc. All rights reserved.

Correlation of diffusion and perfusion MRI with Ki-67 in high-grade meningiomas.

PubMed

Ginat, Daniel T; Mangla, Rajiv; Yeaney, Gabrielle; Wang, Henry Z

2010-12-01

Atypical and anaplastic meningiomas have a greater likelihood of recurrence than benign meningiomas. The risk for recurrence is often estimated using the Ki-67 labeling index. The purpose of this study was to determine the correlation between Ki-67 and regional cerebral blood volume (rCBV) and between Ki-67 and apparent diffusion coefficient (ADC) in atypical and anaplastic meningiomas. A retrospective review of the advanced imaging and immunohistochemical characteristics of atypical and anaplastic meningiomas was performed. The relative minimum ADC, relative maximum rCBV, and specimen Ki-67 index were measured. Pearson's correlation was used to compare these parameters. There were 23 cases with available ADC maps and 20 cases with available rCBV maps. The average Ki-67 among the cases with ADC maps and rCBV maps was 17.6% (range, 5-38%) and 16.7% (range, 3-38%), respectively. The mean minimum ADC ratio was 0.91 (SD, 0.26) and the mean maximum rCBV ratio was 22.5 (SD, 7.9). There was a significant positive correlation between maximum rCBV and Ki-67 (Pearson's correlation, 0.69; p = 0.00038). However, there was no significant correlation between minimum ADC and Ki-67 (Pearson's correlation, -0.051; p = 0.70). Maximum rCBV correlated significantly with Ki-67 in high-grade meningiomas.

Sudden post-traumatic sciatica caused by a thoracic spinal meningioma.

PubMed

Mariniello, Giuseppe; Malacario, Francesca; Dones, Flavia; Severino, Rocco; Ugga, Lorenzo; Russo, Camilla; Elefante, Andrea; Maiuri, Francesco

2016-10-01

Spinal meningiomas usually present with slowly progressive symptoms of cord and root compression, while a sudden clinical onset is very rare. A 35-year-old previously symptom-free woman presented sudden right sciatica and weakness of her right leg following a fall with impact to her left foot. A neurological examination showed paresis of the right quadriceps, tibial and sural muscles, increased bilateral knee and ankle reflexes and positive Babinski sign. Magnetic resonance imaging (MRI) revealed the presence of a spinal T11 meningioma in the left postero-lateral compartment of the spinal canal; at this level, the spinal cord was displaced to the contralateral side with the conus in the normal position. At surgery, a meningioma with dural attachment of the left postero-lateral dural surface was removed. The intervention resulted in rapid remission of both pain and neurological deficits. Spinal meningiomas may exceptionally present with sudden pain and neurological deficits as result of tumour bleeding or post-traumatic injury of the already compressed nervous structures, both in normal patients and in those with conus displacement or tethered cord. In this case, the traumatic impact of the left foot was transmitted to the spine, resulting in stretching of the already compressed cord and of the contralateral lombosacral roots. This case suggests that low thoracic cord compression should be suspected in patients with post-traumatic radicular leg pain with normal lumbar spine MRI. © The Author(s) 2016.

Reticular Appearance on Gadolinium-enhanced T1- and Diffusion-weighted MRI, and Low Apparent Diffusion Coefficient Values in Microcystic Meningioma Cysts.

PubMed

Terada, Yukinori; Toda, Hiroki; Okumura, Ryosuke; Ikeda, Naokado; Yuba, Yoshiaki; Katayama, Toshiro; Iwasaki, Koichi

2018-03-01

Microcystic meningioma, a rare meningioma subtype, can present diagnostic difficulty. We aimed to investigate the historadiological properties of microcystic meningioma using conventional magnetic resonance imaging (MRI) and diffusion-weighted imaging (DWI) analysis. We retrospectively analyzed conventional MRI and DWI results of six microcystic meningioma cases by examining their appearance and determining their apparent diffusion coefficient (ADC) values. The ADC values of the intratumoral components were normalized with ADC values of the cerebrospinal fluid in the lateral ventricle (ADC ratios). As cystic formations are frequently associated with microcystic meningiomas, their MRI characteristics were compared with the imaging data from 11 cystic meningiomas of non-microcystic subtypes. We found that cysts in microcystic meningioma tended to have a reticular appearance on DWI, as they did on gadolinium-enhanced T1-weighted imaging. Additionally, these reticular cysts had significantly lower ADC ratios than microcystic non-reticular and non-microcystic cysts. These DWI characteristics likely reflect the histological properties of microcystic meningioma. A reticular appearance on gadolinium-enhanced T1-weighted MRI and DWI, and cyst formation with relatively low ADC values can be diagnostic markers of microcystic meningiomas.

Serum TIMP1 and TIMP2 concentration in patients with different grades of meningioma.

PubMed

Mashayekhi, Farhad; Saberi, Alia; Mashayekhi, Sohail

2018-07-01

Meningiomas are common primary brain tumors that constitute about 13% of all intracranial tumors. Matrix metalloproteinase-9 (MMP-9) is able to degrade the extracellular matrix and basement membrane leading to cancer cell invasion and metastasis. MMPs are specifically inhibited by a family of small extracellular proteins known as the tissue inhibitors of metalloproteinases (TIMPs). The objective of this project was to evaluate serum concentration of TIMP-1 and TIMP-2 in patients with different grades of meningioma. Ninety samples from different stages of patients with meningitis (42 cases of grade I, 28 grade II, 20 grade III) and 51 samples from normal healthy were included in this study. Total protein concentration (TPC) and the level TIMP-1 and TIMP-2 serum were determined by Bio-Rad protein assay based on the Bradford dye procedure and enzyme-linked immunosorbent assay (ELISA), respectively. No significant change in the TPC was seen in the serum of patients with meningioma when compared with normal controls. Results obtained demonstrated that all serum samples presented TIMP-1 and TIMP-2 expression, whereas, starting from grade I to III meningiomas, a significant decrease of TIMP-1 and TIMP-2 expression was observed as compared to controls. The results of this study show that a low expression of TIMP1 and TIMP2 is correlated with advanced stages of meningioma. It is also concluded that the detection of serum TIMP1 and TIMP2 may be useful in classifying different grades of meningioma. Copyright © 2018 Elsevier B.V. All rights reserved.

Meningiomas: Objective assessment of proliferative indices by immunohistochemistry and automated counting method.

PubMed

Chavali, Pooja; Uppin, Megha S; Uppin, Shantveer G; Challa, Sundaram

2017-01-01

The most reliable histological correlate of recurrence risk in meningiomas is increased mitotic activity. Proliferative index with Ki-67 immunostaining is a helpful adjunct to manual counting. However, both show considerable inter-observer variability. A new immunohistochemical method for counting mitotic figures, using antibody against the phosphohistone H3 (PHH3) protein was introduced. Similarly, a computer based automated counting for Ki-67 labelling index (LI) is available. To study the use of these new techniques in the objective assessment of proliferation indices in meningiomas. This was a retrospective study of intracranial meningiomas diagnosed during the year 2013.The hematoxylin and eosin (H and E) sections and immunohistochemistry (IHC) with Ki-67 were reviewed by two pathologists. Photomicrographs of the representative areas were subjected to Ki-67 analysis by Immunoratio (IR) software. Mean Ki-67 LI, both manual and by IR were calculated. IHC with PHH3 was performed. PHH3 positive nuclei were counted and mean values calculated. Data analysis was done using SPSS software. A total of 64 intracranial meningiomas were diagnosed. Evaluation on H and E, PHH3, Ki-67 LI (both manual and IR) were done in 32 cases (22 grade I and 10 grade II meningiomas). Statistically significant correlation was seen between the mitotic count in each grade and PHH3 values and also between the grade of the tumor and values of Ki-67 and PHH3. Both the techniques used in the study had advantage over, as well as, correlated well with the existing techniques and hence, can be applied to routine use.

Preformed titanium cranioplasty after resection of skull base meningiomas - a technical note.

PubMed

Schebesch, Karl-Michael; Höhne, Julius; Gassner, Holger G; Brawanski, Alexander

2013-12-01

Meningiomas of the fronto-basal skull are difficult to manage as the treatment usually includes extensive resection of the lesion, consecutive reconstruction of the meninges and of the skull. Especially after removal of spheno-orbital and sphenoid-wing meningiomas, the cosmetic result is of utmost importance. In this technical note, we present our institutional approach in the treatment of skull base meningiomas, focussing on the reconstruction of the neurocranium with individually preformed titanium cranioplasty (CRANIOTOP(®), CL Instruments, Germany). Two female patients (40 years, 64 years) are presented. Both patients presented with skull base lesions suggestive of meningiomas. The preoperative thin-sliced CT scan was processed to generate a 3D-model of the skull. On it, the resection was mapped and following a simulated resection, the cranioplasty was manufactured. Intra-operatively, the titanium plate served as a template for the skull resection and was implanted after microsurgical tumour removal, consecutively. The cosmetic result was excellent. Immediate postoperative CT scan revealed accurate fitting and complete tumour removal. Control Magnetic Resonance Imaging (MRI) within 12 weeks was possible without any artifacts. The comprehensive approach described indicates only one surgical procedure for tumour removal and for reconstruction of the skull. The titanium plate served as an exact template for complete resection of the osseous parts of the tumour. Cosmetic outcome was excellent and control MRI was possible post operatively. CRANIOTOP(®) cranioplasty is a safe and practical tool for reconstruction of the skull after meningioma surgery. Copyright © 2013 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

Gadobutrol Versus Gadopentetate Dimeglumine or Gadobenate Dimeglumine Before DCE-MRI in Diagnosing Patients With Multiple Sclerosis, Grade II-IV Glioma, or Brain Metastases

ClinicalTrials.gov

2017-03-22

Adult Anaplastic (Malignant) Meningioma; Adult Anaplastic Astrocytoma; Adult Anaplastic Ependymoma; Adult Anaplastic Oligodendroglioma; Adult Brain Stem Glioma; Adult Choroid Plexus Neoplasm; Adult Diffuse Astrocytoma; Adult Ependymoblastoma; Adult Ependymoma; Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Adult Grade II Meningioma; Adult Medulloblastoma; Adult Mixed Glioma; Adult Oligodendroglioma; Adult Papillary Meningioma; Adult Pineal Gland Astrocytoma; Adult Pineoblastoma; Adult Primary Melanocytic Lesion of Meninges; Adult Supratentorial Primitive Neuroectodermal Tumor; Malignant Adult Intracranial Hemangiopericytoma; Metastatic Malignant Neoplasm in the Brain; Multiple Sclerosis; Recurrent Adult Brain Neoplasm

[A case of petrous ridge meningioma manifested as pneumocephalus followed by Eustachian tube insufflation].

PubMed

Yamaguchi, Shinya; Gi, Hidefuku; Uno, Jyunji; Ikai, Yoshiaki; Inoha, Satoshi; Nagaoka, Shintarou; Nishio, Shunji

2009-05-01

A 50-year-old female, who had a headache after Eustachian tube insufflation for her ear congestion, came to our hospital. CT and MRI revealed pneumocephalus and petrous ridge meningioma which destroyed petrous bone and air cells. Eustachian tube insufflation was considered to make the air coming into the middle ear, mastoid air cell and then into the intracranial space destroying the tumor. At surgery, there was subdural hematoma around the tumor. Total removal of the tumor and the hematoma membrane was performed. Histologically, the tumor was transitional meningioma and the cluster of meningioma cells were noted in the subdural hematoma membrane.

Visual Outcome in Meningiomas Around Anterior Visual Pathways Treated With Linear Accelerator Fractionated Stereotactic Radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stiebel-Kalish, Hadas, E-mail: kalishhadas@gmail.com; Sackler School of Medicine, Tel Aviv University, Tel Aviv; Reich, Ehud

Purpose: Meningiomas threatening the anterior visual pathways (AVPs) and not amenable for surgery are currently treated with multisession stereotactic radiotherapy. Stereotactic radiotherapy is available with a number of devices. The most ubiquitous include the gamma knife, CyberKnife, tomotherapy, and isocentric linear accelerator systems. The purpose of our study was to describe a case series of AVP meningiomas treated with linear accelerator fractionated stereotactic radiotherapy (FSRT) using the multiple, noncoplanar, dynamic conformal rotation paradigm and to compare the success and complication rates with those reported for other techniques. Patients and Methods: We included all patients with AVP meningiomas followed up atmore » our neuro-ophthalmology unit for a minimum of 12 months after FSRT. We compared the details of the neuro-ophthalmologic examinations and tumor size before and after FSRT and at the end of follow-up. Results: Of 87 patients with AVP meningiomas, 17 had been referred for FSRT. Of the 17 patients, 16 completed >12 months of follow-up (mean 39). Of the 16 patients, 11 had undergone surgery before FSRT and 5 had undergone FSRT as first-line management. Tumor control was achieved in 14 of the 16 patients, with three meningiomas shrinking in size after RT. Two meningiomas progressed, one in an area that was outside the radiation field. The visual function had improved in 6 or stabilized in 8 of the 16 patients (88%) and worsened in 2 (12%). Conclusions: Linear accelerator fractionated RT using the multiple noncoplanar dynamic rotation conformal paradigm can be offered to patients with meningiomas that threaten the anterior visual pathways as an adjunct to surgery or as first-line treatment, with results comparable to those reported for other stereotactic RT techniques.« less

Cytological and cytogenetical studies on brain tumors. VI. No evidence for a translocation in 22-monosomic meningiomas.

PubMed

Zankl, H; Weiss, A F; Zang, K D

1975-12-23

The recently detected reciprocal translocations in chronic myeloic leucemia (CML) and Burkitt's lymphoma (BL) made it necessary to clarify if meningiomas really show the described monosomy 22 or also a translocation. In 10 out of 12 meningiomas a total or partial translocation of the missing chromosome 22 to another chromosome could be ruled out by fluorescence banding analysis. Two meningiomas showed marker chromosomes of such a complex composition that it was impossible to decide if a 22 translocation was present or not. From these results it was concluded that meningioma cells, in contrast to CML and BL, show almost regularly a loss of a definitive part of their genome.

Endoscopic endonasal approaches for the management of skull base meningiomas. Selection criteria and clinical outcomes.

PubMed

Todeschini, Alexandre B; Otto, Bradley A; Carrau, Ricardo L; Prevedello, Daniel M

2018-05-28

Meningiomas are the most common primary intracranial tumor, arising from different locations, including the skull base. Despite advances in adjuvant treatments, surgical resection remains the main and best treatment for meningiomas. New surgical strategies, such as the endoscopic endonasal approach, have greatly contributed in achieving maximum and total safe resection, preserving the patient's neurological function. Based on the senior authors large experience and a review of the current literature, we have compiled this chapter. We review the surgical technique used at our institution and the most relevant aspects of patient selection when considering resecting a skull base meningioma using the the EEA. Further consideration is given to some skull base meningiomas arising from specific locations with some case examples. The EEA is not an ideal approach for every skull base meningioma. Careful evaluation of the surrounding neurovascular structures surrounding the tumor is imperative to select the appropriate surgical corridor for a safe resection. Nevertheless, for appropriately selected cases, the endoscopic technique is a very valuable tool with some evidences of being superior to the microscopic transcranial approach. A dual-trained surgeon, in both endoscopic and transcranial approaches, is the best alternative to achieve the best patient outcome.

Correlation between dynamic contrast-enhanced perfusion MRI relative cerebral blood volume and vascular endothelial growth factor expression in meningiomas.

PubMed

Ginat, Daniel T; Mangla, Rajiv; Yeaney, Gabrielle; Schaefer, Pamela W; Wang, Henry

2012-08-01

To determine whether there is a correlation between vascular endothelial growth factor (VEGF) expression and cerebral blood flow (CBV) measurements in dynamic contrast-enhanced susceptibility perfusion magnetic resonance imaging (MRI) and to correlate the perfusion characteristics in high- versus low-grade meningiomas. A total of 48 (24 high-grade and 24 low-grade) meningiomas with available dynamic susceptibility-weighted MRI were retrospectively reviewed for maximum CBV and semiquantitative VEGF immunoreactivity. Correlation between normalized CBV and VEGF was made using the Spearman rank test and comparison between CBV in high- versus low-grade meningiomas was made using the Wilcoxon test. There was a significant (P = .01) correlation between normalized maximum CBV and VEGF scores with a Spearman correlation coefficient of 0.37. In addition, there was a significant (P < .01) difference in normalized maximum CBV ratios between high-grade meningiomas (mean 12.6; standard deviation 5.2) and low-grade meningiomas (mean 8.2; standard deviation 5.2). The data suggest that CBV accurately reflects VEGF expression and tumor grade in meningiomas. Perfusion-weighted MRI can potentially serve as a useful biomarker for meningiomas, pending prospective studies. Copyright © 2012 AUR. Published by Elsevier Inc. All rights reserved.

Posterior fossa meningiomas: surgical experience in 161 cases.

PubMed

Roberti, F; Sekhar, L N; Kalavakonda, C; Wright, D C

2001-07-01

We report the clinical, radiological, and surgical findings of patients with posterior fossa meningiomas surgically treated at our institution over the last 6 years. We reviewed 161 consecutive cases of posterior fossa meningiomas operated on between April 1993 and April 1999 at The George Washington University Medical Center. There were 128 female and 33 male patients (mean age 47 years, range of 10-81 years). Meningiomas were classified as petroclival (110 cases), foramen magnum (21 cases), cerebellar hemispheric, lateral tentorial (14 cases), cerebellopontine angle (9 cases), and jugular foramen (7 cases). Mean tumor equivalent diameter (TED) = (D1xD2xDE)(1/3) was 3.1 cm (range of 0.53-8.95). Head pain (50% of cases) and disturbance of gait (44%) were the most common presenting symptoms, and cranial neuropathies the most common neurological signs on admission. Mean preoperative performance status (Karnofsky scale) was 80.2 (range 40-100). Surgical approaches to these tumors included partial labyrinthectomy petrous apicectomy, fronto-temporal/fronto-temporal orbitozygomatic osteotomy, retrosigmoidal, extreme lateral, transpetrosal, and combined. In 38 cases a staged procedure was performed. Gross-total resection was achieved in 57% of patients, and subtotal/partial in 43%. Surgical mortality was 2.5% and complications were encountered in 41% of patients. Postoperative CSF leak occurred in 22 cases (13.6%). The mean follow-up was 19 months, ranging from 0.2 to 63.6, and the mean performance status of patients with a follow-up of at least 12 months was 77 (range of 40-100). Recurrence or progression of disease was found in 13.7% of cases (follow-up 2 years or more). Our experience suggests that although posterior fossa meningiomas represent a continuing challenge for contemporary neurosurgeons, such tumors may be completely or subtotally removed with low rate of mortality and acceptable morbidity, allowing most of these patients to achieve a good outcome in a long

EMMPRIN expression positively correlates with WHO grades of astrocytomas and meningiomas.

PubMed

Tsai, Wen-Chiuan; Chen, Ying; Huang, Li-Chun; Lee, Herng-Sheng; Ma, Hsin-I; Huang, Shih-Ming; Sytwu, Huey-Kang; Hueng, Dueng-Yuan

2013-09-01

High-grade primary brain tumors possessed poor outcome due to invasiveness. Extracellular matrix metalloproteinase inducer (EMMPRIN) stimulates peri-tumoral fibroblasts to secrete matrix metalloproteinase and promote invasiveness. This study hypothesized that high-grade brain tumors overexpress EMMPRIN. Analyzing the public delinked database from the Gene Expression Omnibus profile, the results showed that the EMMPRIN mRNA level was higher in WHO grade IV (n = 81) than in grade III (n = 19, p < 0.0005) astrocytomas and non-tumor brain tissue controls (n = 23, p < 0.00001). The results of tissue microarray-based immunohistochemical (IHC) staining revealed that EMMPRIN levels positively correlated with WHO grades for astrocytomas (p = 0.008) and meningiomas (p = 0.048). EMMPRIN mRNA levels in conventional glioma cell lines (n = 36) was not less than those in glioma primary culture cells (n = 27) and glioblastoma stem-like cells (n = 12). The GBM8401, U87MG, and LN229 human glioma cell lines also overexpressed EMMPRIN. Hematoxylin and eosin, IHC, and immunofluorescence staining of xenografts confirmed that high-grade brain tumors overexpressed EMMPRIN. Lastly, Kaplan-Meier analysis revealed poorer survival in WHO grade IV (n = 56) than in grade III astrocytomas (n = 21, by log-rank test; p = 0.0001, 95 % CI: 1.842-3.053). However, in high-grade astrocytomas, there was no difference in survival between high and low EMMPRIN mRNA levels. Thus, this study identified that high-grade brain tumors overexpress EMMPRIN, which positively correlates with WHO grades in human astrocytomas and meningiomas, and suggests that EMMPRIN may be a therapeutic target of brain tumor.

Isolated Extracranial Intraosseous Metastasis of an Intracranial Meningioma following Bevacizumab Therapy: Case Report and Review of the Literature

PubMed Central

Mukherjee, Debraj; Hu, Jethro L.; Chu, Ray M.

2018-01-01

Meningiomas account for a significant proportion of all primary intracranial tumors; distant metastasis is quite rare. We report a patient with resected, atypical meningioma. The patient's clinical course over 5 years included two craniotomies, a course of radiation, and a shortened course of bevacizumab. Only 5 months after starting bevacizumab, the patient developed an isolated left clavicular pathological fracture attributable to metastatic anaplastic meningioma. This constitutes the first report of meningioma with isolated extracranial intraosseous metastasis in the modern English literature and highlights concerns associated with the use of anti-angiogenic agents in promoting more invasive tumor phenotypes upon disease recurrence. PMID:29492134

Targeting eradication of malignant cells derived from human bone marrow mesenchymal stromal cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yang, Yingbin; School of Life Science, Southwest University, Chongqing 400715; Cai, Shaoxi, E-mail: sxcai@cqu.edu.cn

2010-12-10

Human bone marrow mesenchymal stromal cells (hBMSC) have been shown to participate in malignant transformation. However, hampered by the low frequency of malignant transformation of hBMSC, we do not yet know how to prevent malignant transformation of implanted hBMSC. In this study, in order to establish a model for the eradication of hBMSC-derived malignant cells, a gene fusion consisting of a human telomerase (hTERT) promoter modified with both c-Myc and myeloid zinc finger protein2 (MZF-2) binding elements and followed by the E. coli cytosine deaminase (CD) and luciferase genes was stably transferred into hBMSC via lentiviral transduction; n-phosphonacelyl-L-aspartic acid (PALA)more » selection was used to generate malignant cell colonies derived from transduced hBMSC after treatment with the carcinogenic reagent BPDE. Cells that were amplified after PALA selection were used for transplantation and 5-FC pro-drug cytotoxicity tests. The results showed that PALA-resistant malignant cells could be generated from hBMSC co-induced with lentiviral transduction and treatment with Benzo(a)pyrene Diol Epoxide (BPDE); the modification of c-Myc and MZF-2 binding elements could remarkably enhance the transcriptional activities of the hTERT promoter in malignant cells, whereas transcriptional activity was depressed in normal hBMSC; malignant cells stably expressing CD under the control of the modified hTERT promoter could be eliminated by 5-FC administration. This study has provided a method for targeted eradication of malignant cells derived from hBMSC.« less

An intraventricular clear cell meningioma revealed by an inflammatory syndrome in a male adult: a case report.

PubMed

Cassereau, J; Lavigne, C; Michalak-Provost, S; Ghali, A; Dubas, F; Fournier, H D

2008-07-01

Intraventricular meningiomas are infrequent intracranial tumors. Clinical symptoms are mainly due to an increased intracranial pressure or a direct pressure on the surrounding brain structures. Inflammatory syndrome was described in some patients with chordoid meningiomas. Here we report a case of right intraventricular clear cell meningioma in a 50-year-old man who presented with fever, headache, and inflammatory syndrome. Clinical and biological normalization was rapidly obtained after tumor removal. Immunohistochemical examination showed tumor cells and lymphocytes positivity for the pyrogenic cytokine interleukin-6, with a same intensity. To our knowledge, this is the first case described in the literature concerning an adult man with an intraventricular clear cell meningioma associated with a systemic inflammatory syndrome.

Application of CUSA Excel ultrasonic aspiration system in resection of skull base meningiomas.

PubMed

Tang, Hailiang; Zhang, Haishi; Xie, Qing; Gong, Ye; Zheng, Mingzhe; Wang, Daijun; Zhu, Hongda; Chen, Xiancheng; Zhou, Liangfu

2014-12-01

Here, we introduced our short experience on the application of a new CUSA Excel ultrasonic aspiration system, which was provided by Integra Lifesciences corporation, in skull base meningiomas resection. Ten patients with anterior, middle skull base and sphenoid ridge meningioma were operated using the CUSA Excel ultrasonic aspiration system at the Neurosurgery Department of Shanghai Huashan Hospital from August 2014 to October 2014. There were six male and four female patients, aged from 38 to 61 years old (the mean age was 48.5 years old). Five cases with tumor located at anterior skull base, three cases with tumor on middle skull base, and two cases with tumor on sphenoid ridge. All the patents received total resection of meningiomas with the help of this new tool, and the critical brain vessels and nerves were preserved during operations. All the patients recovered well after operation. This new CUSA Excel ultrasonic aspiration system has the advantage of preserving vital brain arteries and cranial nerves during skull base meningioma resection, which is very important for skull base tumor operations. This key step would ensure a well prognosis for patients. We hope the neurosurgeons would benefit from this kind of technique.

Optic nerve sheath meningiomas.

PubMed

Saeed, Peerooz; Rootman, Jack; Nugent, Robert A; White, Valerie A; Mackenzie, Ian R; Koornneef, Leo

2003-10-01

To study the natural history and growth of optic nerve sheath meningiomas and evaluate their management outcome. Clinicopathologic retrospective noncomparative case series. A retrospective study of 88 patients who were treated between 1976 and 1999 at the University of British Columbia and the University of Amsterdam. Clinical reports, imaging studies, and histopathologic findings were reviewed. The mean age at onset of symptoms was 40.3 years, and most were seen in middle-aged females. Patients typically presented with visual loss, frequently associated with optic atrophy or papilledema and occasionally optociliary shunt vessels. On imaging, the optic nerve demonstrated segmental or diffuse thickening of the sheath or globular growth. Calcification was seen in 31% of cases and was associated with slower tumor growth. Tumors with posterior components in the orbit had more frequent intracranial involvement. Intracranial extension was more frequent and had a greater growth rate in younger patients. Irregular margins in the orbit implied local invasion. A presenting visual acuity better than 20/50 correlated with longer preservation of vision. Patients who underwent radiotherapy showed improvement in their visual acuity, and tumor growth was halted. Optic sheath decompression did not preserve vision. En bloc tumor excision was associated with no detectable recurrence in contrast to debulked tumors that recurred. Meningiomas show characteristic indolent growth. Management therefore should be conservative in most cases. Radiotherapy is indicated in patients with progressive visual deterioration. Surgery, when indicated, should be an en bloc excision.

Nanomelatonin triggers superior anticancer functionality in a human malignant glioblastoma cell line

NASA Astrophysics Data System (ADS)

Yadav, Sanjeev Kumar; Srivastava, Anup Kumar; Dev, Atul; Kaundal, Babita; Choudhury, Subhasree Roy; Karmakar, Surajit

2017-09-01

Melatonin (MEL) has promising medicinal value as an anticancer agent in a variety of malignancies, but there are difficulties in achieving a therapeutic dose due to its short half-life, low bioavailability, poor solubility and extensive first-pass metabolism. In this study chitosan/tripolyphosphate (TPP) nanoparticles were prepared by an ionic gelation method to overcome the therapeutic challenges of melatonin and to improve its anticancer efficacy. Characterization of the melatonin-loaded chitosan (MEL-CS) nanoformulation was performed using transmission and scanning electron microscopies, dynamic light scattering, Fourier transform infrared spectroscopy, Raman spectroscopy and x-ray diffraction. In vitro release, cellular uptake and efficacy studies were tested for their enhanced anticancer potential in human U87MG glioblastoma cells. Confocal studies revealed higher cellular uptake of MEL-CS nanoparticles and enhanced anticancer efficacy in human malignant glioblastoma cancer cells than in healthy non-malignant human HEK293T cells in mono- and co-culture models. Our study has shown for the first time that MEL-CS nanocomposites are therapeutically more effective as compared to free MEL at inducing functional anticancer efficacy in the human brain tumour U87MG cell line.

Intracranial solitary fibrous tumors/hemangiopericytomas: first report of malignant progression.

PubMed

Apra, Caroline; Mokhtari, Karima; Cornu, Philippe; Peyre, Matthieu; Kalamarides, Michel

2018-06-01

OBJECTIVE Meningeal solitary fibrous tumors/hemangiopericytomas (MSFTs/HPCs) are rare intracranial tumors resembling meningiomas. Their classification was redefined in 2016 by the World Health Organization (WHO) as benign Grade I fibrohyaline type, intermediate Grade II hypercellular type, and malignant highly mitotic Grade III. This grouping is based on common histological features and identification of a common NAB2-STAT6 fusion. METHODS The authors retrospectively identified 49 cases of MSFT/HPC. Clinical data were obtained from the medical records, and all cases were analyzed according to this new 2016 WHO grading classification in order to identify malignant transformations. RESULTS Recurrent surgery was performed in 18 (37%) of 49 patients. Malignant progression was identified in 5 (28%) of these 18 cases, with 3 Grade I and 2 Grade II tumors progressing to Grade III, 3-13 years after the initial surgery. Of 31 Grade III tumors treated in this case series, 16% (5/31) were proved to be malignant progressions from lower-grade tumors. CONCLUSIONS Low-grade MSFTs/HPCs can transform into higher grades as shown in this first report of such progression. This is a decisive argument in favor of a common identity for MSFT and meningeal HPC. High-grade MSFTs/HPCs tend to recur more often and be associated with reduced overall survival. Malignant progression could be one mechanism explaining some recurrences or metastases, and justifying long-term follow-up, even for patients with Grade I tumors.

Volumetric response of intracranial meningioma after photon or particle irradiation.

PubMed

Mozes, Petra; Dittmar, Jan Oliver; Habermehl, Daniel; Tonndorf-Martini, Eric; Hideghety, Katalin; Dittmar, Anne; Debus, Jürgen; Combs, Stephanie E

2017-03-01

Meningiomas are usually slow growing, well circumscribed intracranial tumors. In symptom-free cases observation with close follow-up imaging could be performed. Symptomatic meningiomas could be surgically removed and/or treated with radiotherapy. The study aimed to evaluate the volumetric response of intracranial meningiomas at different time points after photon, proton, and a mixed photon and carbon ion boost irradiation. In Group A 38 patients received proton therapy (median dose: 56 GyE in 1.8-2 GyE daily fractions) or a mixed photon/carbon ion therapy (50 Gy in 2 Gy daily fractions with intensity modulated radiotherapy (IMRT) and 18 GyE in 3 GyE daily dose carbon ion boost). Thirty-nine patients (Group B) were treated by photon therapy with IMRT or fractionated stereotactic radiotherapy technique (median dose: 56 Gy in 1.8-2 Gy daily fractions). The delineation of the tumor volume was based on the initial, one- and two-year follow-up magnetic resonance imaging and these volumes were compared to evaluate the volumetric tumor response. Significant tumor volume shrinkage was detected at one- and at two-year follow-up both after irradiation by particles and by photons. No significant difference in tumor volume change was observed between photon, proton or combined photon plus carbon ion boost treated patients. WHO grade and gender appear to be determining factors for tumor volume shrinkage. Significant volumetric shrinkage of meningiomas could be observed independently of the applied radiation modality. Long-term follow-up is recommended to evaluate further dynamic of size reduction and its correlation with outcome data.

AR Signaling in Human Malignancies: Prostate Cancer and Beyond.

PubMed

Antonarakis, Emmanuel S

2018-01-18

The notion that androgens and androgen receptor (AR) signaling are the hallmarks of prostate cancer oncogenesis and disease progression is generally well accepted. What is more poorly understood is the role of AR signaling in other human malignancies. This special issue of Cancers initially reviews the role of AR in advanced prostate cancer, and then explores the potential importance of AR signaling in other epithelial malignancies. The first few articles focus on the use of novel AR-targeting therapies in castration-resistant prostate cancer and the mechanisms of resistance to novel antiandrogens, and they also outline the interaction between AR and other cellular pathways, including PI3 kinase signaling, transcriptional regulation, angiogenesis, stromal factors, Wnt signaling, and epigenetic regulation in prostate cancer. The next several articles review the possible role of androgens and AR signaling in breast cancer, bladder cancer, salivary gland cancer, and hepatocellular carcinoma, as well as the potential treatment implications of using antiandrogen therapies in these non-prostatic malignancies.

Análisis comparativo de meningiomas cerebrales Grado I vs Grado II en una serie retrospectiva de 63 pacientes operados

PubMed Central

Coppola, Federico; Campbell, Juan Iaconis; Herrero, Juan Manuel; Volpe, Emilio; Cersosimo, Tito

2017-01-01

Resumen Introducción: Los meningiomas Grado II tienen un comportamiento biológico más agresivo que los Grado I. A partir del año 2007, con los nuevos criterios de clasificación, la incidencia de meningiomas atípicos reportada aumentó hasta un 35%. Objetivo: Establecer diferencias entre los Meningiomas Grado I y II de la clasificación de la OMS, en lo que respecta a: grados de resección de Simpson, localización tumoral, necesidad de reintervención, tratamiento adyuvante, evolución y mortalidad. Métodos: Estudio retrospectivo de 63 pacientes operados entre el periodo 2009-2015. Variables analizadas: sexo, edad, grado histológico, localización, grado de resección quirúrgica, radioterapia adyuvante, mortalidad y evolución. Resultados: Se analizaron 63 pacientes: 51 Grado I y 12 Grado II de la clasificación de la OMS. La distribución por sexo no mostró diferencias entre meningiomas benignos y atípicos. Tampoco el grupo etario de presentación; mediana de 57 años. Un 55% de los meningiomas benignos se localizaron fuera de la base del cráneo versus el 91,6% de los meningiomas atípicos (P = 0.02). En el 74,5% de los meningiomas benignos se logró una resección total (Simpson I-II-III) versus el 58.3% para los atípicos (P = 0.3). Se reintervinieron el 33,3% de meningiomas atípicos en comparación con el 9.8% de los benignos (P = 0.03). Tuvieron una buena evolución el 86,2% de los benignos vs el 53,8% de los GII (P = 0.01). Realizaron radioterapia adyuvante el 33,3% de los meningiomas Grado II vs el 1,9% de los Grado I. Conclusiones: Los meningiomas atípicos cerebrales tienen peor pronóstico evolutivo que los Grado I de la OMS. Presentan una mayor tasa de reintervención y se localizan más frecuentemente fuera de la base del cráneo. La localización pareciera ser un factor de riesgo para el desarrollo de meningiomas atípicos. PMID:29142779

Application of CUSA Excel ultrasonic aspiration system in resection of skull base meningiomas

PubMed Central

Tang, Hailiang; Zhang, Haishi; Xie, Qing; Zheng, Mingzhe; Wang, Daijun; Zhu, Hongda; Chen, Xiancheng; Zhou, Liangfu

2014-01-01

Background Here, we introduced our short experience on the application of a new CUSA Excel ultrasonic aspiration system, which was provided by Integra Lifesciences corporation, in skull base meningiomas resection. Methods Ten patients with anterior, middle skull base and sphenoid ridge meningioma were operated using the CUSA Excel ultrasonic aspiration system at the Neurosurgery Department of Shanghai Huashan Hospital from August 2014 to October 2014. There were six male and four female patients, aged from 38 to 61 years old (the mean age was 48.5 years old). Five cases with tumor located at anterior skull base, three cases with tumor on middle skull base, and two cases with tumor on sphenoid ridge. Results All the patents received total resection of meningiomas with the help of this new tool, and the critical brain vessels and nerves were preserved during operations. All the patients recovered well after operation. Conclusions This new CUSA Excel ultrasonic aspiration system has the advantage of preserving vital brain arteries and cranial nerves during skull base meningioma resection, which is very important for skull base tumor operations. This key step would ensure a well prognosis for patients. We hope the neurosurgeons would benefit from this kind of technique. PMID:25561762

Stereotactic fractionated radiotherapy for the treatment of benign meningiomas

DOE Office of Scientific and Technical Information (OSTI.GOV)

Candish, Charles; McKenzie, Michael; Clark, Brenda G.

Purpose: To assess the use of stereotactic fractionated radiotherapy (SRT) for the treatment of meningiomas. Methods and Materials: Between April 1999 and October 2004, 38 patients underwent SRT. Of 34 patients (36 tumors) assessed, the median age was 53 years. The indication was primary treatment in 26 cases (no histology) and postoperative in 10 cases. The most common sites were cavernous sinus (17), optic nerve (6), and cerebellopontine angle (5). The median gross target volume and planning target volume were 8.9 cm{sup 3} and 18.9 cm{sup 3}, respectively. Stereotactic treatment was delivered with 6-MV photons with static conformal fields (custom-mademore » blocks, 9 patients, and micromultileaf collimator, 25 patients). Median number of fields was six. The median dose prescribed was 50 Gy (range, 45-50.4 Gy) in 28 fractions. The median homogeneity and conformality indices were 1.1 and 1.79, respectively. Results: Treatment was well tolerated. Median follow-up was 26 months with 100% progression-free survival. One patient developed an area of possible radionecrosis related to previous radiotherapy, and 2 men developed mild hypogonadism necessitating testosterone replacement. The vision of 5 of 6 patients with optic pathway meningiomas improved or remained static. Conclusions: Stereotactic fractionated radiotherapy for the treatment of meningiomas is practical, and with early follow-up, seems to be effective.« less

Curvularia fungi presenting as a large cranial base meningioma: case report.

PubMed

Singh, Harminder; Irwin, Sibyl; Falowski, Steven; Rosen, Mark; Kenyon, Lawrence; Jungkind, Donald; Evans, James

2008-07-01

Fungal infections are emerging as a growing threat to human health, especially in immunocompromised patients. Candida, Cryptococcus, and Aspergillus are a few of the commonly encountered organisms leading to brain abscesses. In this report, we describe Curvularia geniculata as the causative agent in central nervous system infection. Our review of the literature did not reveal a similar published case of central nervous system infection with this organism. A 35-year-old African-American man presented with obstructive hydrocephalus from a large cranial base lesion. Imaging characteristics on computed tomographic and magnetic resonance imaging scans were consistent with those of a cranial base meningioma. The patient underwent an endoscopic transnasal/transclival approach to the anterior middle cranial base for biopsy and decompression of this lesion. A spindle cell proliferation was observed on frozen section, which favored a diagnosis of meningioma. However, on permanent sections, we identified fungal hyphae with budding. Subsequent biopsies grew Curvularia in fungal cultures. Deoxyribonucleic acid sequencing was used to confirm the identification of the isolate as Curvularia geniculata. Limited data are available for in vitro susceptibility testing of Curvularia, and treatment modalities have not yet been standardized. The prognosis is usually poor. Despite being treated with voriconazole and intravenous amphotericin, this patient progressed to multiorgan failure and ultimately died. This is the first reported case of central nervous system infection by Curvularia geniculata.

Meningiomas: A Comparative Study of 68Ga-DOTATOC, 68Ga-DOTANOC and 68Ga-DOTATATE for Molecular Imaging in Mice

PubMed Central

Soto-Montenegro, María Luisa; Peña-Zalbidea, Santiago; Mateos-Pérez, Jose María; Oteo, Marta; Romero, Eduardo; Morcillo, Miguel Ángel; Desco, Manuel

2014-01-01

Purpose The goal of this study was to compare the tumor uptake kinetics and diagnostic value of three 68Ga-DOTA-labeled somatostatin analogues (68Ga-DOTATOC, 68Ga-DOTANOC, and 68Ga-DOTATATE) using PET/CT in a murine model with subcutaneous meningioma xenografts. Methods The experiment was performed with 16 male NUDE NU/NU mice bearing xenografts of a human meningioma cell line (CH-157MN). 68Ga-DOTATOC, 68Ga-DOTANOC, and 68Ga-DOTATATE were produced in a FASTLab automated platform. Imaging was performed on an Argus small-animal PET/CT scanner. The SUVmax of the liver and muscle, and the tumor-to-liver (T/L) and tumor-to-muscle (T/M) SUV ratios were computed. Kinetic analysis was performed using Logan graphical analysis for a two-tissue reversible compartmental model, and the volume of distribution (Vt) was determined. Results Hepatic SUVmax and Vt were significantly higher with 68Ga-DOTANOC than with 68Ga-DOTATOC and 68Ga-DOTATATE. No significant differences between tracers were found for SUVmax in tumor or muscle. No differences were found in the T/L SUV ratio between 68Ga-DOTATATE and 68Ga-DOTATOC, both of which had a higher fraction than 68Ga-DOTANOC. The T/M SUV ratio was significantly higher with 68Ga-DOTATATE than with 68Ga-DOTATOC and 68Ga-DOTANOC. The Vt for tumor was higher with 68Ga-DOTATATE than with 68Ga-DOTANOC and relatively similar to that of 68Ga-DOTATOC. Conclusions This study demonstrates, for the first time, the ability of the three radiolabeled somatostatin analogues tested to image a human meningioma cell line. Although Vt was relatively similar with 68Ga-DOTATATE and 68Ga-DOTATOC, uptake was higher with 68Ga-DOTATATE in the tumor than with 68Ga-DOTANOC and 68Ga-DOTATOC, suggesting a higher diagnostic value of 68Ga-DOTATATE for detecting meningiomas. PMID:25369268

[Microsurgical removal of olfactory groove meningiomas].

PubMed

Liang, Ri-Sheng; Zhou, Liang-Fu; Mao, Ying; Zhang, Rong; Yang, Wei-Zhong

2011-01-01

To explore an effective method for further improving the surgical results of treatment of olfactory groove meningiomas. Sixty seven cases of olfactory groove meningiomas were treated by microneurosurgery, among which fifty seven were de novo cases, eight were recurrent tumors and the other two re-recurrent cases. Modified Derome approach was used in 12 cases, bilateral subfrontal approach in 28 cases, modified pterional approach in 21 cases and unilateral subfrontal approach in six cases. Tumors were resected microsurgically with radical removal of invaded dura, bone, and paranasal sinus mucosa. Reconstruction was performed in patients with skull base defect. Simpson grade I removal was accomplished in 59 cases, grade II in seven cases and grade IV in one case. Among 57 patients with de novo tumor, Simpson I resection was accomplished in 54 cases. Postoperative rhinorrhea and intracranial infection occurred in one case and was cured after temporal lumbar CSF drainage and antibiotic therapy. Two patients (2.9%) died within one month after operation, i.e.one aged patient of heart failure and the other of severe hypothalamus complication. Forty seven patients (72.3%) were followed up from one to ten years with an average of five years and four months. With the exception of two cases died, among the alive 45 patients, there were only three patients with tumor recurrence, which had undergone Simpson II or IV tumor resection. No recurrence was found in cases with Simpson I tumor removal. Previous blurred vision was not improved in three patients, hemiparalysis in two patients, and the other patients recovered well, resuming previous jobs or being able to take care themselves. Total tumor removal (Simpson I) should be the surgical goal for treatment of olfactory groove meningiomas, especially for de novo cases. An appropriate approach is fundamental in the effort to remove an OGM totally. Appropriate anterior skull base reconstruction with vascularized material is

Is there an increased rate of additional malignancies in patients with mantle cell lymphoma?

PubMed

Barista, I; Cabanillas, F; Romaguera, J E; Khouri, I F; Yang, Y; Smith, T L; Strom, S S; Medeiros, L J; Hagemeister, F B

2002-02-01

To examine the frequency of additional neoplasms preceding and following the diagnosis of mantle cell lymphoma (MCL). A total of 156 patients with MCL treated on the hyperfractionated cyclophosphamide, vincristine, doxorubicin and dexamethasone alternated with methotrexate and cytosine arabinoside (Hyper-CVAD/M-A) program with or without rituximab from 1994 to 2000 were the subjects of this report. These patients were followed for a median time of 26 months, and a total of 32 (21%) additional neoplasms were diagnosed, 21 preceding the diagnosis of MCL and 11 following MCL. After excluding certain types of non-invasive neoplasms, including basal cell carcinoma, meningioma and cervical intraepithelial neoplasia, we observed seven second malignancies after the diagnosis of MCL, and the 5-year cumulative incidence rate of second malignancy was 11%. The observed-to-expected (O/E) ratio was 7/0.07 = 100 [95% confidence interval (CI) 49.3 to 186.6; P <0.0001]. Of the 21 malignancies diagnosed prior to MCL, 16 were invasive and five non-invasive. There were a total of 10 urologic malignancies occurring before or after the diagnosis of MCL was established. Our findings suggest that there is an increased incidence of second malignancies in patients with MCL. In addition, the high number of cases with urinary tract cancer in our series may substantiate prior reports describing a possible association between lymphoma and urologic malignancies.

Boron neutron capture therapy for recurrent high-grade meningiomas.

PubMed

Kawabata, Shinji; Hiramatsu, Ryo; Kuroiwa, Toshihiko; Ono, Koji; Miyatake, Shin-Ichi

2013-10-01

Similar to glioblastomas, high-grade meningiomas are difficult pathologies to control. In this study, the authors used boron neutron capture therapy (BNCT), a tumor-selective intensive particle radiation modality, to treat high-grade meningioma. From June 2005 to September 2011, BNCT was applied 28 times in 20 cases of recurrent high-grade meningioma. All patients had previously undergone intensive treatments such as repetitive surgeries and multiple sessions of radiation therapy. Fluorine-18-labeled boronophenylalanine ((18)F-BPA) PET was performed before BNCT in 19 of the 20 cases; BPA is itself a therapeutic compound. Compound uptake, tumor shrinkage, long-term control rate including survival time, and failure pattern of the treated patients were all evaluated. Eighteen of 19 cases studied using (18)F-BPA PET showed good BPA uptake, with ratios of tumor to normal brain greater than 2.7. These ratios indicated the likely effects of BNCT prior to neutron irradiation. The original tumor sizes were between 4.3 cm(3) and 109 cm(3). A mean tumor volume reduction of 64.5% was obtained after BNCT within just 2 months. The median follow-up duration was 13 months. Six patients are still alive; at present, the median survival times after BNCT and diagnosis are 14.1 months (95% CI 8.6-40.4 months) and 45.7 months (95% CI 32.4-70.7 months), respectively. Clinical symptoms before BNCT, such as hemiparesis and facial pain, were improved after BNCT in symptomatic cases. Systemic metastasis, intracranial distant recurrence outside the radiation field, CSF dissemination, and local tumor progression were observed in 6, 7, 3, and 3 cases, respectively, during the clinical course. Apparent pseudoprogression was observed in at least 3 cases. Symptomatic radiation injuries occurred in 6 cases, and were controllable in all but 1 case. Boron neutron capture therapy may be especially effective in cases of high-grade meningioma.

Fractionated Proton Radiotherapy for Benign Cavernous Sinus Meningiomas

DOE Office of Scientific and Technical Information (OSTI.GOV)

Slater, Jerry D., E-mail: jdslater@dominion.llumc.edu; Loredo, Lilia N.; Chung, Arthur

2012-08-01

Purpose: To evaluate the efficacy of fractionated proton radiotherapy for a population of patients with benign cavernous sinus meningiomas. Methods and Materials: Between 1991 and 2002, 72 patients were treated at Loma Linda University Medical Center with proton therapy for cavernous sinus meningiomas. Fifty-one patients had biopsy or subtotal resection; 47 had World Health Organization grade 1 pathology. Twenty-one patients had no histologic verification. Twenty-two patients received primary proton therapy; 30 had 1 previous surgery; 20 had more than 1 surgery. The mean gross tumor volume was 27.6 cm{sup 3}; mean clinical target volume was 52.9 cm{sup 3}. Median totalmore » doses for patients with and without histologic verification were 59 and 57 Gy, respectively. Mean and median follow-up periods were 74 months. Results: The overall 5-year actuarial control rate was 96%; the control rate was 99% in patients with grade 1 or absent histologic findings and 50% for those with atypical histology. All 21 patients who did not have histologic verification and 46 of 47 patients with histologic confirmation of grade 1 tumor demonstrated disease control at 5 years. Control rates for patients without previous surgery, 1 surgery, and 2 or more surgeries were 95%, 96%, and 95%, respectively. Conclusions: Fractionated proton radiotherapy for grade 1 cavernous sinus meningiomas achieves excellent control rates with minimal toxicities, regardless of surgical intervention or use of histologic diagnosis. Disease control for large lesions can be achieved by primary fractionated proton therapy.« less

Sensitivity and usefulness of anti-phosphohistone-H3 antibody immunostaining for counting mitotic figures in meningioma cases.

PubMed

Fukushima, Shintaro; Terasaki, Mizuhiko; Sakata, Kiyohiko; Miyagi, Naohisa; Kato, Seiya; Sugita, Yasuo; Shigemori, Minoru

2009-01-01

According to current World Health Organization (WHO) criteria, counting mitotic figures (MF), which is equal to the mitotic index (MI), on paraffin sections stained with hematoxylin and eosin (HE) is one of the recognized classification methods for meningiomas. However, it is not always easy to find the area of highest mitotic activity, and there are different perspectives among pathologists with regard to differentiating MF from non-MF, i.e., which are apoptotic figures and which are crushed or distorted cells. Moreover, there is an issue of overgrading in meningiomas with preoperative feeder embolization. Recently, anti-phosphohistone-H3 (PHH3) antibody has been reported as a mitosis-specific marker for meningioma grading. In this study, we attempted PHH3 immunostaining for our meningioma cases and verified not only the sensitivity of PHH3 immunostaining but also that of its usefulness in grading meningiomas. Forty-five initial histologically confirmed meningiomas (37 benign, 7 atypical, and 1 anaplastic) were reviewed according to current WHO criteria based on counting MF on HE-stained slides. PHH3-immunostained MF were counted in the same way, and the MIB-1 labeling index (LI) was calculated for each sample. PHH3-labeled MF were easily identified and permitted rapid recognition of the areas of highest mitotic activity. As a result, significant increase of PHH3 mitotic index (PHH3-MI) in comparison with HE mitotic index (HE-MI) and strong correlations with HE-MI to PHH3-MI as well as PHH3-MI to MIB-1 LI were demonstrated. Furthermore, no significant differences of PHH3-MI between cases with and without feeder embolization were demonstrated. As such, PHH3 may be a sensitive and useful marker for meningioma grading as based on the MF.

Fusion of magnetic resonance angiography and magnetic resonance imaging for surgical planning for meningioma--technical note.

PubMed

Kashimura, Hiroshi; Ogasawara, Kuniaki; Arai, Hiroshi; Beppu, Takaaki; Inoue, Takashi; Takahashi, Tsutomu; Matsuda, Koichi; Takahashi, Yujiro; Fujiwara, Shunrou; Ogawa, Akira

2008-09-01

A fusion technique for magnetic resonance (MR) angiography and MR imaging was developed to help assess the peritumoral angioarchitecture during surgical planning for meningioma. Three-dimensional time-of-flight (3D-TOF) and 3D-spoiled gradient recalled (SPGR) datasets were obtained from 10 patients with intracranial meningioma, and fused using newly developed volume registration and visualization software. Maximum intensity projection (MIP) images from 3D-TOF MR angiography and axial SPGR MR imaging were displayed at the same time on the monitor. Selecting a vessel on the real-time MIP image indicated the corresponding points on the axial image automatically. Fusion images showed displacement of the anterior cerebral or middle cerebral artery in 7 patients and encasement of the anterior cerebral arteries in 1 patient, with no relationship between the main arterial trunk and tumor in 2 patients. Fusion of MR angiography and MR imaging can clarify relationships between the intracranial vasculature and meningioma, and may be helpful for surgical planning for meningioma.

Stereotactic radiosurgery of World Health Organization grade II and III intracranial meningiomas: treatment results on the basis of a 22-year experience.

PubMed

Pollock, Bruce E; Stafford, Scott L; Link, Michael J; Garces, Yolanda I; Foote, Robert L

2012-02-15

A study was undertaken to define the variables associated with tumor control and survival after single-session stereotactic radiosurgery (SRS) for patients with atypical and malignant intracranial meningiomas. Fifty patients with World Health Organization (WHO) grade II (n = 37) or grade III (n = 13) meningiomas underwent SRS from 1990 to 2008. Most tumors were located in the falx/parasagittal region or cerebral convexities (n = 35, 70%). Twenty patients (40%) had progressing tumors despite prior external beam radiation therapy (EBRT) (median dose, 54.0 grays [Gy]). The median treatment volume was 14.6 cm(3) ; the median tumor margin dose was 15.0 Gy. Seven patients (14%) received concurrent EBRT (median dose, 50.4 Gy). Follow-up (median, 38 months) was censored at last evaluation (n = 28) or death (n = 22). Tumor grade correlated with disease-specific survival (DSS) (hazard ratio [HR], 3.4; P = .008), local tumor control (HR, 2.4; P = .02), and progression-free survival (PFS) (HR, 2.6; P = .02) on univariate analysis, but not on multivariate analysis. Multivariate analysis showed that having failed EBRT and tumor volume >14.6 cm(3) were negative predictors of DSS and local control (HR, 3.0; P = .02 and HR, 4.4; P = .01; HR, 3.3; P = .001 and HR, 2.3; P = .02;, respectively). Having failed EBRT was a negative predictor of PFS (HR, 3.5; P = .002). Thirteen patients (26%) had radiation-related complications at a median of 6 months after radiosurgery. Tumor progression despite prior EBRT and larger tumor volume are negative predictors of tumor control and survival for patients having SRS for WHO grade II and III intracranial meningiomas. Copyright © 2011 American Cancer Society.

Gamma Knife radiosurgery for posterior fossa meningiomas: a multicenter study.

PubMed

Sheehan, Jason P; Starke, Robert M; Kano, Hideyuki; Barnett, Gene H; Mathieu, David; Chiang, Veronica; Yu, James B; Hess, Judith; McBride, Heyoung L; Honea, Norissa; Nakaji, Peter; Lee, John Y K; Rahmathulla, Gazanfar; Evanoff, Wendi A; Alonso-Basanta, Michelle; Lunsford, L Dade

2015-06-01

Posterior fossa meningiomas represent a common yet challenging clinical entity. They are often associated with neurovascular structures and adjacent to the brainstem. Resection can be undertaken for posterior fossa meningiomas, but residual or recurrent tumor is frequent. Stereotactic radiosurgery (SRS) has been used to treat meningiomas, and this study evaluates the outcome of this approach for those located in the posterior fossa. At 7 medical centers participating in the North American Gamma Knife Consortium, 675 patients undergoing SRS for a posterior fossa meningioma were identified, and clinical and radiological data were obtained for these cases. Females outnumbered males at a ratio of 3.8 to 1, and the median patient age was 57.6 years (range 12-89 years). Prior resection was performed in 43.3% of the patient sample. The mean tumor volume was 6.5 cm(3), and a median margin dose of 13.6 Gy (range 8-40 Gy) was delivered to the tumor. At a mean follow-up of 60.1 months, tumor control was achieved in 91.2% of cases. Actuarial tumor control was 95%, 92%, and 81% at 3, 5, and 10 years after radiosurgery. Factors predictive of tumor progression included age greater than 65 years (hazard ratio [HR] 2.36, 95% CI 1.30-4.29, p = 0.005), prior history of radiotherapy (HR 5.19, 95% CI 1.69-15.94, p = 0.004), and increasing tumor volume (HR 1.05, 95% CI 1.01-1.08, p = 0.005). Clinical stability or improvement was achieved in 92.3% of patients. Increasing tumor volume (odds ratio [OR] 1.06, 95% CI 1.01-1.10, p = 0.009) and clival, petrous, or cerebellopontine angle location as compared with petroclival, tentorial, and foramen magnum location (OR 1.95, 95% CI 1.05-3.65, p = 0.036) were predictive of neurological decline after radiosurgery. After radiosurgery, ventriculoperitoneal shunt placement, resection, and radiation therapy were performed in 1.6%, 3.6%, and 1.5%, respectively. Stereotactic radiosurgery affords a high rate of tumor control and neurological preservation

Meningioma presenting as temporal region swelling: Diagnosis by cytopathology and immunohistochemical confirmation on cell block preparation

PubMed Central

Nair, Anila Kunjulekshmi Amma Raveendran; Nayak, Nileena; Kattoor, Jayasree

2015-01-01

Meningiomas are common intracranial neoplasms. Meningomas are rarely subjected to fine-needle aspiration (FNA) studies. However, intraoperative squash preparations are commonly done. FNA of meningiomas are usually performed incidentally for cases with a clinical suspicion of some other disease such as metastatic carcinoma. We are reporting two cases, which were referred to our center with a diagnosis of metastatic carcinoma on FNA from swelling of the temporal region. We are discussing the characteristic cytomorphological features, which help in diagnosing meningiomas, the common cytological differentials, and the utility of immunohistochemistry (IHC) on cell block preparations in confirming the diagnosis, especially when there is a clinical differential diagnosis. PMID:26729986

Computerized morphometry as an aid in distinguishing recurrent versus nonrecurrent meningiomas.

PubMed

Noy, Shawna; Vlodavsky, Euvgeni; Klorin, Geula; Drumea, Karen; Ben Izhak, Ofer; Shor, Eli; Sabo, Edmond

2011-06-01

To use novel digital and morphometric methods to identify variables able to better predict the recurrence of intracranial meningiomas. Histologic images from 30 previously diagnosed meningioma tumors that recurred over 10 years of follow-up were consecutively selected from the Rambam Pathology Archives. Images were captured and morphometrically analyzed. Novel algorithms of digital pattern recognition using Fourier transformation and fractal and nuclear texture analyses were applied to evaluate the overall growth pattern complexity of the tumors, as well as the chromatin texture of individual tumor nuclei. The extracted parameters were then correlated with patient prognosis. Kaplan-Meier analyses revealed statistically significant associations between tumor morphometric parameters and recurrence times. Tumors with less nuclear orientation, more nuclear density, higher fractal dimension, and less regular chromatin textures tended to recur faster than those with a higher degree of nuclear order, less pattern complexity, lower density, and more homogeneous chromatin nuclear textures (p < 0.01). To our knowledge, these digital morphometric methods were used for the first time to accurately predict tumor recurrence in patients with intracranial meningiomas. The use of these methods may bring additional valuable information to the clinician regarding the optimal management of these patients.

BCR expression is decreased in meningiomas showing loss of heterozygosity of 22q within a new minimal deletion region.

PubMed

Wozniak, K; Piaskowski, S; Gresner, S M; Golanska, E; Bieniek, E; Bigoszewska, K; Sikorska, B; Szybka, M; Kulczycka-Wojdala, D; Zakrzewska, M; Zawlik, I; Papierz, W; Stawski, R; Jaskolski, D J; Och, W; Sieruta, M; Liberski, P P; Rieske, P

2008-05-01

Neurofibromin 2 (NF2), located on chromosome arm 22q, has been established as a tumor suppressor gene involved in meningioma pathogenesis. In our study, we investigated 149 meningiomas to determine whether there are additional tumor suppressor genes localized on chromosome 22q, apart from NF2, that might be involved in meningioma pathogenesis. The LOH analysis on chromosome 22q identified two regions of deletion: the first one, which is limited to the NF2 gene locus, and the second one, which is outside this location. The new minimal deletion region (MDR) included the following genes: BCR (breakpoint cluster region), RAB36 (a member of RAS oncogene family), GNAZ [guanine nucleotide binding protein (G protein), alpha-z polypeptide], and RTDR1 (rhabdoid tumor deletion region gene 1). The expression levels of all these genes, including NF2, were subsequently analyzed by quantitative real-time polymerase chain reaction. We observed a significantly lowered expression level of NF2 in meningiomas with 22q loss of heterozygosity (LOH) within NF2 region compared to the one in meningiomas with 22q retention of heterozygosity (ROH, P<0.05). Similarly, BCR showed a significantly lowered expression in meningiomas with 22q LOH within the new MDR compared to cases with 22q ROH (P<0.05). Our data, together with the already published information considering BCR function suggest that BCR can be considered as a candidate tumor suppressor gene localized on chromosome 22q which may be involved in meningioma pathogenesis.

Calvarial Plasmacytoma Mimicking Meningioma as the Initial Presentation of Multiple Myeloma

PubMed Central

Pisapia, David; Ramakrishna, Rohan

2017-01-01

Plasmacytoma of the calvarium is a well-described feature of multiple myeloma and in some cases has been reported as a solitary lesion. However, when associated with multiple myeloma these are typically identified after the initial diagnosis is made. This case is unusual in that the diagnosis of plasmacytoma was first suspected in a patient thought to have a meningioma on the day of surgery, when a magnetic resonance imaging (MRI) demonstrated spontaneous involution of the mass. Recognition of evolving changes in a calvarial or dural-based lesion should prompt the practitioner to consider alternative diagnoses other than meningioma prior to proceeding with surgical resection. PMID:28465873

Modified temporal approach for a rostro-temporal basal meningioma in a cat.

PubMed

Forterre, Franck; Jaggy, André; Rohrbach, Helene; Dickomeit, Marc; Konar, Martin

2009-06-01

An 11-year-old neutered female domestic shorthair indoor cat was presented to our hospital for treatment of a left-sided rostro-temporal basal meningioma. Focal seizures in the facial muscles had been observed sporadically for 1 year. Two weeks prior to presentation the cat had developed generalised seizures and was treated with symptomatic anticonvulsive treatment. Focal facial seizures, especially on the right side, persisted after medical therapy. From the computed tomography scan, a basal meningioma was suspected by the treating veterinarian. A left-sided suprazygomatical temporobasal approach to the zygomatic arch was chosen because it causes less soft tissue damage. After craniotomy, durotomy and gentle dorsal retraction of the left piriform lobe, the meningioma was removed. Postoperative magnetic resonance imaging confirmed complete excision of the tumour. One day after surgery the cat was alert and a left-sided facial nerve palsy was noticed. Otherwise the neurological examination was normal. Anticonvulsive and eye moistening therapy was continued for 3 months. Six months after surgery the cat was clinically normal without any recurrence of seizures.

Allergic conditions and risk of glioma and meningioma in the CERENAT case-control study.

PubMed

Pouchieu, Camille; Raherison, Chantal; Piel, Clément; Migault, Lucile; Carles, Camille; Fabbro-Perray, Pascale; Loiseau, Hugues; Guillamo, Jean-Sébastien; Lebailly, Pierre; Baldi, Isabelle

2018-06-01

Inverse association between allergic conditions and glioma risk has been consistently reported in epidemiological studies with little attention paid to potential environmental confounders; the association with meningioma risk is less consistent. We examined the association between allergy history and risk of glioma and meningioma in adults using data from the CERENAT (CEREbral tumors: a NATional study) multicenter case-control study carried out in 4 areas in France in 2004-2010. Participants' histories of doctor-diagnosed allergic asthma, eczema, rhinitis/hay fever and other allergic conditions were collected at onset through a detailed questionnaire delivered in a face-to-face interview. Conditional logistic regression for matched sets was adjusted for participants' educational level and mobile phone use. A total of 273 glioma cases, 218 meningioma cases and 982 matched controls selected from the local electoral rolls were analyzed. A significant inverse association was found between glioma and a history of any allergy (OR 0.52, 95% CI 0.36-0.75), with a dose-effect relationship with the number of allergic conditions reported (p-trend = 0.001) and a particularly strong association with hay fever/allergic rhinitis (OR 0.46, 95% CI 0.30-0.72). Interestingly, associations with glioma risk were more pronounced in women. For meningioma, no association was observed with overall or specific allergic conditions. Our findings confirmed the inverse association between allergic conditions and glioma risk but questioned the role of allergy in meningioma risk. Future research is needed to clarify the biological mechanism of overall allergy and allergic rhinitis on glioma and to confirm the different effect by gender.

Genetic and epigenetic alteration of the NF2 gene in sporadic meningiomas.

PubMed

Lomas, Jesus; Bello, M Josefa; Arjona, Dolores; Alonso, M Eva; Martinez-Glez, Victor; Lopez-Marin, Isabel; Amiñoso, Cinthia; de Campos, Jose M; Isla, Alberto; Vaquero, Jesus; Rey, Juan A

2005-03-01

The role of the NF2 gene in the development of meningiomas has recently been documented; inactivating mutations plus allelic loss at 22q, the site of this gene (at 22q12), have been identified in both sporadic and neurofibromatosis type 2-associated tumors. Although epigenetic inactivation through aberrant CpG island methylation of the NF2 5' flanking region has been documented in schwannoma (another NF2-associated neoplasm), data on participation of this epigenetic modification in meningiomas are not yet widely available. Using methylation-specific PCR (MSP) plus sequencing, we assessed the presence of aberrant promoter NF2 methylation in a series of 88 meningiomas (61 grade I, 24 grade II, and 3 grade III), in which the allelic constitution at 22q and the NF2 mutational status also were determined by RFLP/microsatellite and PCR-SSCP analyses. Chromosome 22 allelic loss, NF2 gene mutation, and aberrant NF2 promoter methylation were detected in 49%, 24%, and 26% of cases, respectively. Aberrant NF2 methylation with loss of heterozygosity (LOH) at 22q was found in five cases, and aberrant methylation with NF2 mutation in another; LOH 22q and the mutation were found in 16 samples. The aberrant methylation of the NF2 gene also was the sole alteration in 15 samples, most of which were from grade I tumors. These results indicate that aberrant NF2 hypermethylation may participate in the development of a significant proportion of sporadic meningiomas, primarily those of grade I.

Health-related quality of life of cranial WHO grade I meningioma patients: are current questionnaires relevant?

PubMed

Zamanipoor Najafabadi, Amir H; Peeters, Marthe C M; Lobatto, Daniel J; Broekman, Marieke L D; Smith, Timothy R; Biermasz, Nienke R; Peerdeman, Saskia M; Peul, Wilco C; Taphoorn, Martin J B; van Furth, Wouter R; Dirven, Linda

2017-11-01

The clinical relevance of Health-Related Quality of Life (HRQoL) in meningioma patients has been increasingly acknowledged in recent years. Various questionnaires have been used. However, almost none of these questionnaires has been particularly developed for and/or validated in this patient group. Therefore, the aim of this study was to assess the relevance and comprehensiveness of existing HRQoL questionnaires used in meningioma research and to assess the agreement between patients and health care professionals (HCPs) on the most relevant and important HRQoL issues. A systematic literature search, following the PRISMA statement, was conducted to identify all HRQoL questionnaires used in meningioma research. Semi-structured interviews were organized with patients and HCPs to (1) assess the relevance of all issues covered by the questionnaires (score 0-3: not relevant-highly relevant), (2) assess the ten most important issues, and (3) identify new relevant HRQoL issues. Fourteen different questionnaires were found in the literature, comprising 140 unique issues. Interviews were conducted with 20 patients (median age 57, 71% female) and 10 HCPs (4 neurosurgeons, 2 neurologists, 2 radiotherapists, 1 rehabilitation specialist, 1 neuropsychologist; median experience 13 years). Meningioma patients rated 17-80% of the issues in each of the questionnaires as relevant, HCPs 90-100%. Patients and HCPs agreed on the relevance of only 49 issues (35%, Cohen's kappa: 0.027). Both patients and HCPs considered lack of energy the most important issue. Patients and HCPs suggested five additional relevant issues not covered by current HRQoL questionnaires. Existing HRQoL questionnaires currently used in meningioma patients do not fully cover all relevant issues to these patients. Agreement between patients and HCPs on the relevance of issues was poor. Both findings support the need to develop and validate a meningioma-specific HRQoL questionnaire.

SU-D-207B-02: Early Grade Classification in Meningioma Patients Combining Radiomics and Semantics Data

DOE Office of Scientific and Technical Information (OSTI.GOV)

Coroller, T; Bi, W; Abedalthagafi, M

Purpose: The clinical management of meningioma is guided by its grade and biologic behavior. Currently, diagnosis of tumor grade follows surgical resection and histopathologic review. Reliable techniques for pre-operative determination of tumor behavior are needed. We investigated the association between imaging features extracted from preoperative gadolinium-enhanced T1-weighted MRI and meningioma grade. Methods: We retrospectively examined the pre-operative MRI for 139 patients with de novo WHO grade I (63%) and grade II (37%) meningiomas. We investigated the predictive power of ten semantic radiologic features as determined by a neuroradiologist, fifteen radiomic features, and tumor location. Conventional (volume and diameter) imaging featuresmore » were added for comparison. AUC was computed for continuous and χ{sup 2} for discrete variables. Classification was done using random forest. Performance was evaluated using cross validation (1000 iterations, 75% training and 25% validation). All p-values were adjusted for multiple testing. Results: Significant association was observed between meningioma grade and tumor location (p<0.001) and two semantic features including intra-tumoral heterogeneity (p<0.001) and overt hemorrhage (p=0.01). Conventional (AUC 0.61–0.67) and eleven radiomic (AUC 0.60–0.70) features were significant from random (p<0.05, Noether test). Median AUC values for classification of tumor grade were 0.57, 0.71, 0.72 and 0.77 respectively for conventional, radiomic, location, and semantic features after using random forest. By combining all imaging data (semantic, radiomic, and location), the median AUC was 0.81, which offers superior predicting power to that of conventional imaging descriptors for meningioma as well as radiomic features alone (p<0.05, permutation test). Conclusion: We demonstrate a strong association between radiologic features and meningioma grade. Pre-operative prediction of tumor behavior based on imaging features

Preoperative Evaluation of Collateral Venous Anastomoses in Meningioma Involving Cerebral Venous Sinus by Susceptibility Weighted Imaging

PubMed Central

Wang, Qing; He, Jingzhen; Ma, Xiangxing

2014-01-01

Abstract Precise preoperative identification of the collateral venous anastomoses is critical for proper surgical management of patients with meningioma involving sinus. This study was to assess the feasibility of susceptibility weighted imaging (SWI) to delineate the collateral venous anastomoses before surgery. Twenty-five patients with meningiomas that were involved in sinuses underwent surgery and the collateral anastomoses were evaluated with SWI and phase-contrast magnetic resonance venography (MRV) before surgery. The results obtained with SWI were compared with those obtained with MRV. Intraoperative findings were used as the gold standard. By surgery, a total of 98 collateral anastomotic veins were identified in the 25 patients. SWI depicted 85 collateral anastomotic veins close to the meningioma with a sensitivity of 87%, whereas MRV showed 57 collateral anastomotic veins with a sensitivity of 58%. The detectability of collateral anastomotic veins in SWI images was superior to MRV. The results suggest that SWI is superior to MRV and could provide more reliable information on the collateral venous anastomoses in patients with meningioma. PMID:25501068

P11.10 Role of hydroxyurea as an adjuvant treatment after gamma knife radiosurgery for atypical (WHO grade II) meningiomas

PubMed Central

Abdel Karim, K.; El Shehaby, A.; Emad, R.; Reda, W.; El Mahdy, M.; Ghali, R.; Nabeel, A.

2016-01-01

Abstract Objective: The use of gamma knife radiosurgery in the treatment of atypical (WHO grade II) meningiomas has been reported in the past with highly variable degrees of success. The use of hydroxyurea as a radiation sensitizer as well as salvage chemotherapy in cancer patients is well established and was also used for treatment of recurrent and malignant meningiomas. In this study we investigated the effect of hydroxyurea administration after gamma knife radiosurgery for atypical (grade II) meningiomas on local tumor control and patient survival. Patients and methods: Between November 2008 and April 2014, thirty-five patients with pathologically proven atypical meningiomas were treated by gamma knife radiosurgery. We excluded patients who had received previous external beam radiotherapy. Twenty-three patients were given hydroxyurea after gamma knife treatment. The rest of the patients refused to take the treatment or were incompliant (were not included in the study). Of these 23, nineteen patients harboring 20 tumors were available for radiological and clinical follow up for a minimum of 2 years. Four patients were lost from follow up. Twenty tumors underwent 26 gamma knife procedures. Five tumors underwent staged treatment. The tumor volume was 0.6–38.3 cc (median 12.7 cc). The prescription dose/session ranged from 10 to 16 Gy (mean 14 Gy). The patients received a course of hydroxyurea (1000 mg/day) for one year after gamma knife treatment. The mean follow up period was 43 months (14–76 months). Results: Tumor control was achieved in 18 out of 20 tumors where 15 tumors shrank and 3 tumors remained stable with a tumor control rate of 90%. Tumor progression occurred in 2 patients (at 14 and 15 months). Transient edema was observed with 6 tumors which was temporary, and no G3 or G4 myelosuppression were recorded. Two patients died from progression of other tumors not included in the study after 3 and 6 years. Distant tumor progression (in another

Yoga Therapy in Treating Patients With Malignant Brain Tumors

ClinicalTrials.gov

2017-07-27

Adult Anaplastic Astrocytoma; Adult Anaplastic Ependymoma; Adult Anaplastic Meningioma; Adult Anaplastic Oligodendroglioma; Adult Brain Stem Glioma; Adult Choroid Plexus Tumor; Adult Diffuse Astrocytoma; Adult Ependymoblastoma; Adult Ependymoma; Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Adult Grade II Meningioma; Adult Medulloblastoma; Adult Meningeal Hemangiopericytoma; Adult Mixed Glioma; Adult Oligodendroglioma; Adult Papillary Meningioma; Adult Pineal Gland Astrocytoma; Adult Pineoblastoma; Adult Pineocytoma; Adult Supratentorial Primitive Neuroectodermal Tumor (PNET); Recurrent Adult Brain Tumor

Phenotypic characterization of telomerase-immortalized primary non-malignant and malignant tumor-derived human prostate epithelial cell lines

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gu Yongpeng; Li Hongzhen; Miki, Jun

2006-04-01

In vitro human prostate cell culture models are critical for clarifying the mechanism of prostate cancer progression and for testing preventive and therapeutic agents. Cell lines ideal for the study of human primary prostate tumors would be those derived from spontaneously immortalized tumor cells; unfortunately, explanted primary prostate cells survive only short-term in culture, and rarely immortalize spontaneously. Therefore, we recently have generated five immortal human prostate epithelial cell cultures derived from both the benign and malignant tissues of prostate cancer patients with telomerase, a gene that prevents cellular senescence. Examination of these cell lines for their morphologies and proliferativemore » capacities, their abilities to grow in low serum, to respond to androgen stimulation, to grow above the agar layer, to form tumors in SCID mice, suggests that they may serve as valid, useful tools for the elucidation of early events in prostate tumorigenesis. Furthermore, the chromosome alterations observed in these immortalized cell lines expressing aspects of the malignant phenotypes imply that these cell lines accurately recapitulate the genetic composition of primary tumors. These novel in vitro models may offer unique models for the study of prostate carcinogenesis and also provide the means for testing both chemopreventive and chemotherapeutic agents.« less

Dumbbell meningioma of the cervico-clavicular region.

PubMed

Hlavka, V; Miklić, P; Besenski, N; Miklić, D; Franz, G

1991-01-01

The authors are reporting on a case of a 55-year-old man with an epidural meningioma in the region from the C VII. to the Th I. segment. The tumor encircled this region, and to the front and right involved the channels through which pass the C VI, C VII. and C VIII. roots. Subdurally, no tumoral mass was found. Another part of this tumor, of the same histological architecture as the epidural cervicospinal part was found in the supraclavicular region to the right, closely connected to the arteries and nerves of this region. The authors discuss the possibility of the tumoral occurrence at this site, primarily taking into account the origin of this tumor from the cells of the outer surface of the arachnoidea, i.e. cap cells which can invade the dura, with later separation from the main arachnoidal layer. The other possibility of such dumbbell meningioma occurring at the outgoing openings of the neural paths from the spinal channel should be looked for in the remnants of the arachnoidal cells in the region of the outgoing openings. In the paper are also discussed and correlated clinico-pathological, CT and angiographic findings.

Evaluating the Quality and Readability of Internet Information on Meningiomas.

PubMed

Saeed, Fozia; Anderson, Ian

2017-01-01

The Internet is a highly powerful resource for patients and provides an extensive amount of information on medical conditions. It is therefore important that the information accessible is accurate, up to date, and at an appropriate comprehensive level for the general public. This article aims to evaluate the quality of patient information on meningiomas. The term meningioma was searched using the following search engines: Google, Bing, Yahoo, Ask, and AOL. The top 100 meningioma Web sites were analyzed for readability using the Flesch Reading Ease score and the Flesch-Kincaid grade level. The quality of each Web page was assessed with the DISCERN instrument and the Centers for Disease Control and Prevention (CDC) Clear Communication Index (CCI). The quality of information on the Internet on meningiomas is highly variable. The overall mean Flesch Reading Ease score was 43.1 (standard deviation = 13.3) and the mean Flesch-Kincaid grade of all the Web sites was 11.2 (standard deviation = 2.3). This finding suggests that the information is on average difficult to read. Only one Web site was at the recommended seventh-grade level and the remainder were above this grade. Only one third of the Web pages had Health On the Net Code of Conduct or The Information Standard certification and were found to be significantly of higher quality: DISCERN (P = 0.022) and CDC CCI (P = 0.027). More than 50% of the Web sites had significantly poor or average DISCERN scores and only 2 Web sites fulfilled the CDC CCI criteria. It is recommended that clinicians personally research material for their patients to be able to guide them to reliable and accurate Web sites. It is also encouraged to become Health On the Net Code of Conduct/The Information Standard certified because this may indicate information of high quality. In addition, it is also recommended that authors of existing information assess the quality of their online health information against the CDC CCI criteria. Crown

[Linear accelerator-based stereotactic radiation treatment of patients with medial middle fossa meningiomas].

PubMed

Golanov, A V; Cherekaev, V A; Serova, N K; Pronin, I N; Gorlachev, G E; Kotel'nikova, T M; Podoprigora, A E; Kudriavtseva, P A; Galkin, M V

2010-01-01

Medial middle fossa meningiomas are challenging for neurosurgical treatment. Invasion of cranial nerves and vessels leads to high risk of complications after removal of such meningiomas. Currently methods of conformal stereotactic radiation treatment are applied wider and wider for the discussed lesions. During a 3.5-year period 80 patients with medial middle fossa meningiomas were treated in Burdenko Moscow Neurosurgical Institute using linear accelerator "Novalis". In 31 case radiation treatment was preceded by surgical resection. In majority of patients symptoms included cranial nerve dysfunction: oculomotor disturbances in 62.5%, trigeminal impairment--in 37.5%, visual deficit--in 43.8%, facial nerve palsy--in 1.25%. 74 patients underwent radiotherapy with classical fractioning, 2--in hypofractionated mode and 4 received radiosurgery. In cases of classical fractioning mean marginal dose reached 46.3 Gy during 28-33 fractions, in hypofractioning (7 fractions)--31.5 Gy, in radiosurgery--16.25 Gy. Mean follow-up period was 18.4 months (6-42 months). Control of tumor growth was achieved in 97.5% of cases (78 patients): in 42 (52.5%) lesion shrinked, in 36 (45%) stabilization was observed. Clinical examination revealed improvement of visual function in 15 patients (18%) and deterioration in 2 (2.5%). No new neuropathies were found. Stereotactic radiation treatment is the method of choice for medial anterior and middle fossa meningiomas due to effective control of tumor progression and minimal rate of complications.

Update on treatment modalities for optic nerve sheath meningiomas.

PubMed

Liu, James K; Forman, Scott; Moorthy, Chitti R; Benzil, Deborah L

2003-05-15

Optic nerve sheath meningiomas (ONSMs) represent 1 to 2% of all meningiomas and one third of all optic nerve tumors. The management of ONSMs is controversial. Traditional surgical removal often results in postoperative blindness in the affected eye and thus has been abandoned as a treatment option in most patients. Surgery may be unnecessarily aggressive, especially if the patient has useful vision. When these tumors are left untreated, however, ensuing progressive visual impairment may lead to complete blindness. More recently, radiotherapy has gained wider acceptance as a treatment for these lesions. The authors of some reports have suggested that fractionated stereotactic radiosurgery (SRS) may be the best option for treating primary ONSMs. In patients with documented progressive visual deterioration, fractionated SRS may be effective in improving or stabilizing remaining functional vision. The authors review the clinical presentation, radiographic characteristics, and management of ONSMs, emphasizing the use of fractionated SRS.

Meningioma and bone hyperostosis: expression of bone stimulating factors and review of the literature.

PubMed

Di Cristofori, Andrea; Del Bene, Massimiliano; Locatelli, Marco; Boggio, Francesca; Ercoli, Giulia; Ferrero, Stefano; Del Gobbo, Alessandro

2018-05-02

Several hypothesis have been proposed in order to understand the mechanisms underlying the meningioma related hyperostosis. Objective of our study was to investigate the role of osteoprotegerin(OPG), insulin-like growth factor-1(IGF-1), endothelin-1(ET-1), Bone Morphogenetic Protein(BMP-2 and -4). A total of 149 patients (39 males and 110 females with a mean age of 62 years) that received surgery were included. Depending on the relationship with the bone, meningiomas were classified in hyperostotic, osteolytic, infiltrative and without relation with the bone. Expression of BMP-2,-4; OPG and IGF-1 was evaluated with tissue microarray analysis on the surgical sample. Our series included 132 cases of grade I meningioma, 14 cases of grade II and 3 cases of grade III (according WHO). Relying on pre-operative CT scan the cases were classified as follow: hyperostotic(n=11), osteolytic(n=11), infiltrative(n=15), without relation with the bone(n=108). Four cases were excluded from the statistical analysis. Using ROC curves analysis, we identified a 2% cut-off for IGF-1 mean value that discriminated between osteolytic and osteoblastic lesions: cases with IGF-1 mean expression less than 2% were classified as osteolytic(p=0.0046);while cases with OPG mean expression less than 10% were classified as osteolytic(p=0.048). No other significant relations were found. OPG and IGF-1 found to be associated with development of hyeprostosis. Preliminary findings suggest that hyperostosis can be caused by an overexpression of osteogenic molecules that influence the osteoblast/osteoclast activity. Based on our results, further studies on hyperostotic bony tissue in meningiomas are needed in order to better understand how meningiomas influence the bone overproduction. Copyright © 2018 Elsevier Inc. All rights reserved.

Gamma knife radiosurgery for skull-base meningiomas.

PubMed

Takanashi, Masami; Fukuoka, Seiji; Hojyo, Atsufumi; Sasaki, Takehiko; Nakagawara, Jyoji; Nakamura, Hirohiko

2009-01-01

The primary purpose of this study was to evaluate the efficacy of gamma knife radiosurgery (GKRS) when used as a treatment modality for cavernous sinus or posterior fossa skull-base meningiomas (SBMs), with particular attention given to whether or not intentional partial resection followed by GKRS constitutes an appropriate combination treatment method for larger SBMs. Of the 101 SBM patients in this series, 38 were classified as having cavernous sinus meningiomas (CSMs), and 63 presented with posterior fossa meningiomas (PFMs). The patients with no history of prior surgery (19 CSMs, 57 PFMs) were treated according to a set protocol. Small to medium-sized SBMs were treated by GKRS only. To minimize the risk of functional deficits, larger tumors were treated with the combination of intentional partial resection followed by GKRS. Residual or recurrent tumors in patients who had undergone extirpations prior to GKRS (19 CSMs, 6 PFMs) are not eligible for this treatment method (due to the surgeries not being performed as part of a combination strategy designed to preserve neurological function as the first priority). The mean follow-up period was 51.9 months (range, 6-144 months). The overall tumor control rates were 95.5% in CSMs and 98.4% in PFMs. Nearly all tumors treated with GKRS alone were well controlled and the patients had no deficits. Furthermore, none of the patients who had undergone prior surgeries experienced new neurological deficits after GKRS. While new neurological deficits appeared far less often in those receiving the combination of partial resection with subsequent GKRS, extirpations tended to be associated with not only a higher incidence of new deficits but also a significant increase in the worsening of already-existing deficits. Our results indicate that GKRS is a safe and effective primary treatment for SBMs with small to moderate tumor volumes. We also found that larger SBMs compressing the optic pathway or brain stem can be effectively

Voxel-based lesion mapping of meningioma: a comprehensive lesion location mapping of 260 lesions.

PubMed

Hirayama, Ryuichi; Kinoshita, Manabu; Arita, Hideyuki; Kagawa, Naoki; Kishima, Haruhiko; Hashimoto, Naoya; Fujimoto, Yasunori; Yoshimine, Toshiki

2018-06-01

OBJECTIVE In the present study the authors aimed to determine preferred locations of meningiomas by avoiding descriptive analysis and instead using voxel-based lesion mapping and 3D image-rendering techniques. METHODS Magnetic resonance images obtained in 248 treatment-naïve meningioma patients with 260 lesions were retrospectively and consecutively collected. All images were registered to a 1-mm isotropic, high-resolution, T1-weighted brain atlas provided by the Montreal Neurological Institute (the MNI152), and a lesion frequency map was created, followed by 3D volume rendering to visualize the preferred locations of meningiomas in 3D. RESULTS The 3D lesion frequency map clearly showed that skull base structures such as parasellar, sphenoid wing, and petroclival regions were commonly affected by the tumor. The middle one-third of the superior sagittal sinus was most commonly affected in parasagittal tumors. Substantial lesion accumulation was observed around the leptomeninges covering the central sulcus and the sylvian fissure, with very few lesions observed at the frontal, parietal, and occipital convexities. CONCLUSIONS Using an objective visualization method, meningiomas were shown to be located around the middle third of the superior sagittal sinus, the perisylvian convexity, and the skull base. These observations, which are in line with previous descriptive analyses, justify further use of voxel-based lesion mapping techniques to help understand the biological nature of this disease.

Lateral suboccipital retrosigmoid approach with tentorial incision for petroclival meningiomas: technical note.

PubMed

Yamahata, Hitoshi; Tokimura, Hiroshi; Hirahara, Kazuho; Ishii, Takeshi; Mori, Masanao; Hanaya, Ryosuke; Arita, Kazunori

2014-08-01

Introduction The resection of petroclival meningiomas presents great neurosurgical challenges. Although multiple surgical approaches have been developed, the retrosigmoid route tends to be used to address tumors that are predominantly located in the posterior fossa. Our modification of the lateral suboccipital retrosigmoid approach with the placement of a tentorial incision yields good visualization of the supratentorial part of the tumor around the midbrain. Methods We treated four patients, one with primary and three with recurrent petroclival meningioma, by our modified approach. After lateral suboccipital craniotomy, the infratentorial part of the tumor was removed after detaching it from the tentorial surface. The cerebellar tentorium was then carefully incised from the supracerebellar angle, taking care not to damage the superior cerebellar artery and trochlear nerve. Results The operative field surrounding the midbrain was widened by this procedure, and safe dissection of the tumor from the brainstem and other neurovascular structures was performed with direct observation of the interface. Conclusions Our approach is a useful modification of the retrosigmoid approach to petroclival meningiomas. It facilitates the safe resection of the supratentorial part of the tumor in the ambient cistern behind the tentorium.

5-Aminolevulinic acid-induced protoporphyrin IX fluorescence in meningioma: qualitative and quantitative measurements in vivo.

PubMed

Valdes, Pablo A; Bekelis, Kimon; Harris, Brent T; Wilson, Brian C; Leblond, Frederic; Kim, Anthony; Simmons, Nathan E; Erkmen, Kadir; Paulsen, Keith D; Roberts, David W

2014-03-01

The use of 5-aminolevulinic acid (ALA)-induced protoporphyrin IX (PpIX) fluorescence has shown promise as a surgical adjunct for maximizing the extent of surgical resection in gliomas. To date, the clinical utility of 5-ALA in meningiomas is not fully understood, with most descriptive studies using qualitative approaches to 5-ALA-PpIX. To assess the diagnostic performance of 5-ALA-PpIX fluorescence during surgical resection of meningioma. ALA was administered to 15 patients with meningioma undergoing PpIX fluorescence-guided surgery at our institution. At various points during the procedure, the surgeon performed qualitative, visual assessments of fluorescence by using the surgical microscope, followed by a quantitative fluorescence measurement by using an intraoperative probe. Specimens were collected at each point for subsequent neuropathological analysis. Clustered data analysis of variance was used to ascertain a difference between groups, and receiver operating characteristic analyses were performed to assess diagnostic capabilities. Red-pink fluorescence was observed in 80% (12/15) of patients, with visible fluorescence generally demonstrating a strong, homogenous character. Quantitative fluorescence measured diagnostically significant PpIX concentrations (cPpIx) in both visibly and nonvisibly fluorescent tissues, with significantly higher cPpIx in both visibly fluorescent (P < .001) and tumor tissue (P = .002). Receiver operating characteristic analyses also showed diagnostic accuracies up to 90% for differentiating tumor from normal dura. ALA-induced PpIX fluorescence guidance is a potential and promising adjunct in accurately detecting neoplastic tissue during meningioma resective surgery. These results suggest a broader reach for PpIX as a biomarker for meningiomas than was previously noted in the literature.

5-Aminolevulinic Acid-Induced Protoporphyrin IX Fluorescence in Meningioma: Qualitative and Quantitative Measurements In Vivo

PubMed Central

Valdes, Pablo A.; Bekelis, Kimon; Harris, Brent T.; Wilson, Brian C.; Leblond, Frederic; Kim, Anthony; Simmons, Nathan E.; Erkmen, Kadir; Paulsen, Keith D.; Roberts, David W.

2014-01-01

BACKGROUND The use of 5-aminolevulinic acid (ALA)-induced protoporphyrin IX (PpIX) fluorescence has shown promise as a surgical adjunct for maximizing the extent of surgical resection in gliomas. To date, the clinical utility of 5-ALA in meningiomas is not fully understood, with most descriptive studies using qualitative approaches to 5-ALA-PpIX. OBJECTIVE To assess the diagnostic performance of 5-ALA-PpIX fluorescence during surgical resection of meningioma. METHODS ALA was administered to 15 patients with meningioma undergoing PpIX fluorescence-guided surgery at our institution. At various points during the procedure, the surgeon performed qualitative, visual assessments of fluorescence by using the surgical microscope, followed by a quantitative fluorescence measurement by using an intra-operative probe. Specimens were collected at each point for subsequent neuropathological analysis. Clustered data analysis of variance was used to ascertain a difference between groups, and receiver operating characteristic analyses were performed to assess diagnostic capabilities. RESULTS Red-pink fluorescence was observed in 80% (12/15) of patients, with visible fluorescence generally demonstrating a strong, homogenous character. Quantitative fluorescence measured diagnostically significant PpIX concentrations (CPpIx) in both visibly and nonvisibly fluorescent tissues, with significantly higher CPpIx in both visibly fluorescent (P < .001) and tumor tissue (P = .002). Receiver operating characteristic analyses also showed diagnostic accuracies up to 90% for differentiating tumor from normal dura. CONCLUSION ALA-induced PpIX fluorescence guidance is a potential and promising adjunct in accurately detecting neoplastic tissue during meningioma resective surgery. These results suggest a broader reach for PpIX as a biomarker for meningiomas than was previously noted in the literature. PMID:23887194

Phenotypes and Karyotypes of Human Malignant Mesothelioma Cell Lines

PubMed Central

Relan, Vandana; Morrison, Leanne; Parsonson, Kylie; Clarke, Belinda E.; Duhig, Edwina E.; Windsor, Morgan N.; Matar, Kevin S.; Naidoo, Rishendran; Passmore, Linda; McCaul, Elizabeth; Courtney, Deborah; Yang, Ian A.; Fong, Kwun M.; Bowman, Rayleen V.

2013-01-01

Background Malignant mesothelioma is an aggressive tumour of serosal surfaces most commonly pleura. Characterised cell lines represent a valuable tool to study the biology of mesothelioma. The aim of this study was to develop and biologically characterise six malignant mesothelioma cell lines to evaluate their potential as models of human malignant mesothelioma. Methods Five lines were initiated from pleural biopsies, and one from pleural effusion of patients with histologically proven malignant mesothelioma. Mesothelial origin was assessed by standard morphology, Transmission Electron Microscopy (TEM) and immunocytochemistry. Growth characteristics were assayed using population doubling times. Spectral karyotyping was performed to assess chromosomal abnormalities. Authentication of donor specific derivation was undertaken by DNA fingerprinting using a panel of SNPs. Results Most of cell lines exhibited spindle cell shape, with some retaining stellate shapes. At passage 2 to 6 all lines stained positively for calretinin and cytokeratin 19, and demonstrated capacity for anchorage-independent growth. At passage 4 to 16, doubling times ranged from 30–72 hours, and on spectral karyotyping all lines exhibited numerical chromosomal abnormalities ranging from 41 to 113. Monosomy of chromosomes 8, 14, 22 or 17 was observed in three lines. One line displayed four different karyotypes at passage 8, but only one karyotype at passage 42, and another displayed polyploidy at passage 40 which was not present at early passages. At passages 5–17, TEM showed characteristic features of mesothelioma ultrastructure in all lines including microvilli and tight intercellular junctions. Conclusion These six cell lines exhibit varying cell morphology, a range of doubling times, and show diverse passage-dependent structural chromosomal changes observed in malignant tumours. However they retain characteristic immunocytochemical protein expression profiles of mesothelioma during

Unilateral endonasal transcribriform approach with septal transposition for olfactory groove meningioma: can olfaction be preserved?

PubMed

Youssef, A Samy; Sampath, Raghuram; Freeman, Jacob L; Mattingly, Jameson K; Ramakrishnan, Vijay R

2016-10-01

Loss of olfaction has been considered inevitable in endoscopic endonasal resection of olfactory groove meningiomas. Olfaction preservation may be feasible through an endonasal unilateral transcribriform approach, with the option for expansion using septal transposition and contralateral preservation of the olfactory apparatus. An expanded unilateral endonasal transcribriform approach with septal transposition was performed in five cadaver heads. The approach was applied in a surgical case of a 24 × 26-mm olfactory groove meningioma originating from the right cribriform plate with partially intact olfaction. The surgical approach offered adequate exposure to the anterior skull base bilaterally. The nasal/septal mucosa was preserved on the contralateral side. Gross total resection of the meningioma was achieved with the successful preservation of the contralateral olfactory apparatus and preoperative olfaction. Six months later, the left nasal cavity showed no disruption of the mucosal lining and the right side was at the appropriate stage of healing for a harvested nasoseptal flap. One year later, the preoperative olfactory function was intact and favorably viewed by the patient. Objective testing of olfaction showed microsomia. Olfaction preservation may be feasible in the endoscopic endonasal resection of a unilateral olfactory groove meningioma through a unilateral transcribriform approach with septal transposition and preservation of the contralateral olfactory apparatus.

From Grey Scale B-Mode to Elastosonography: Multimodal Ultrasound Imaging in Meningioma Surgery-Pictorial Essay and Literature Review.

PubMed

Prada, Francesco; Del Bene, Massimiliano; Moiraghi, Alessandro; Casali, Cecilia; Legnani, Federico Giuseppe; Saladino, Andrea; Perin, Alessandro; Vetrano, Ignazio Gaspare; Mattei, Luca; Richetta, Carla; Saini, Marco; DiMeco, Francesco

2015-01-01

The main goal in meningioma surgery is to achieve complete tumor removal, when possible, while improving or preserving patient neurological functions. Intraoperative imaging guidance is one fundamental tool for such achievement. In this regard, intra-operative ultrasound (ioUS) is a reliable solution to obtain real-time information during surgery and it has been applied in many different aspect of neurosurgery. In the last years, different ioUS modalities have been described: B-mode, Fusion Imaging with pre-operative acquired MRI, Doppler, contrast enhanced ultrasound (CEUS), and elastosonography. In this paper, we present our US based multimodal approach in meningioma surgery. We describe all the most relevant ioUS modalities and their intraoperative application to obtain precise and specific information regarding the lesion for a tailored approach in meningioma surgery. For each modality, we perform a review of the literature accompanied by a pictorial essay based on our routinely use of ioUS for meningioma resection.

Survival benefit of postoperative radiation in papillary meningioma: Analysis of the National Cancer Data Base.

PubMed

Sumner, Whitney A; Amini, Arya; Hankinson, Todd C; Foreman, Nicholas K; Gaspar, Laurie E; Kavanagh, Brian D; Karam, Sana D; Rusthoven, Chad G; Liu, Arthur K

2017-01-01

Papillary meningioma represents a rare subset of World Health Organization (WHO) Grade III meningioma that portends an overall poor prognosis. There is relatively limited data regarding the benefit of postoperative radiation therapy (PORT). We used the National Cancer Data Base (NCDB) to compare overall survival (OS) outcomes of surgically resected papillary meningioma cases undergoing PORT compared to post-operative observation. The NCDB was queried for patients with papillary meningioma, diagnosed between 2004 and 2013, who underwent upfront surgery with or without PORT. Overall survival (OS) was determined using the Kaplan-Meier method. Univariate (UVA) and multivariate (MVA) analyses were performed. In total, 190 patients were identified; 89 patients underwent PORT, 101 patients were observed. Eleven patients received chemotherapy (6 with PORT, 5 without). 2-Year OS was significantly improved with PORT vs. no PORT (93.0% vs. 74.4%), as was 5-year OS (78.5% vs. 62.5%) (hazard ratio [HR], 0.48; 95% confidence interval [CI], 0.27-0.85; p  = 0.01). On MVA, patients receiving PORT had improved OS compared to observation (HR, 0.41; 95% CI, 0.22-0.76; p  = 0.005). On subset analysis by age group, the benefit of PORT vs. no PORT was significant in patients ≤18 years ( n  = 13), with 2-year OS of 85.7% vs. 50.0% (HR, 0.08; 95% CI, 0.01-0.80; p  = 0.032) and for patients >18 years ( n  = 184), with 2-year OS of 94.7% vs. 76.1% (HR, 0.55; 95% CI, 0.31-1.00; p  = 0.049), respectively. In this large contemporary analysis, PORT was associated with improved survival for both adult and pediatric patients with papillary meningioma. PORT should be considered in those who present with this rare, aggressive tumor.

Intercellular crosstalk in human malignant melanoma.

PubMed

Dvořánková, Barbora; Szabo, Pavol; Kodet, Ondřej; Strnad, Hynek; Kolář, Michal; Lacina, Lukáš; Krejčí, Eliška; Naňka, Ondřej; Šedo, Aleksi; Smetana, Karel

2017-05-01

Incidence of malignant melanoma is increasing globally. While the initial stages of tumors can be easily treated by a simple surgery, the therapy of advanced stages is rather limited. Melanoma cells spread rapidly through the body of a patient to form multiple metastases. Consequently, the survival rate is poor. Therefore, emphasis in melanoma research is given on early diagnosis and development of novel and more potent therapeutic options. The malignant melanoma is arising from melanocytes, cells protecting mitotically active keratinocytes against damage caused by UV light irradiation. The melanocytes originate in the neural crest and consequently migrate to the epidermis. The relationship between the melanoma cells, the melanocytes, and neural crest stem cells manifests when the melanoma cells are implanted to an early embryo: they use similar migratory routes as the normal neural crest cells. Moreover, malignant potential of these melanoma cells is overdriven in this experimental model, probably due to microenvironmental reprogramming. This observation demonstrates the crucial role of the microenvironment in melanoma biology. Indeed, malignant tumors in general represent complex ecosystems, where multiple cell types influence the growth of genetically mutated cancer cells. This concept is directly applicable to the malignant melanoma. Our review article focuses on possible strategies to modify the intercellular crosstalk in melanoma that can be employed for therapeutic purposes.

The role of steroid receptor coactivator-3 (SRC-3) in human malignant disease.

PubMed

Gojis, O; Rudraraju, B; Alifrangis, C; Krell, J; Libalova, P; Palmieri, C

2010-03-01

The p160 steroid receptor coactivator (SRC) family is critical to the transcriptional activation function of nuclear hormone receptors. A key member of this family is SRC-3, initially found to be amplified and expressed in breast cancer it has subsequent been shown to be expressed in malignant disease arising from a wide range of other organs. An understanding of the potential role of SRC-3 in the pathogenesis and its possible prognostic role in a broad range of tumours will improve our general understanding of carcinogenesis as well as potentially leading to a new prognostic marker as well as new therapeutic targets. Relevant papers were identified by searching the PubMed and MEDLINE databases for article published until 28th February 2009. Only articles published in English were considered. The search terms included "SRC-3", "AIB1" in association with the following terms: "human", "cancer" and "malignant disease". The search focused on malignant disease arising outside of the mammary gland. Full articles were obtained and references were checked for additional material when appropriate. SRC-3 is amplified and expressed in a wide spectrum of human malignant diseases and appears to be a potential prognostic marker in a number of different tumours. SRC-3 appears to be implicated in the possible risk of developing prostate and ovarian cancer. Its presence appears to be a marker of aggressive disease. Further research is required to determine its predictive and prognostic utility given the relative paucity of studies for each specific malignant disease. Copyright (c) 2009. Published by Elsevier Ltd.

Human cytomegalovirus inhibits apoptosis by regulating the activating transcription factor 5 signaling pathway in human malignant glioma cells

PubMed Central

WANG, TONGMEI; QIAN, DONGMENG; HU, MING; LI, LING; ZHANG, LI; CHEN, HAO; YANG, RUI; WANG, BIN

2014-01-01

The activating transcription factor 5 (ATF5), also termed ATFx, is a member of the ATF/cAMP response element-binding protein (CREB) family of basic zipper proteins. ATF5 is an anti-apoptotic protein that is highly expressed in malignant glioma and is essential for glioma cell survival. Accumulating evidence indicates that human malignant gliomas are universally infected with human cytomegalovirus (HCMV). Recent studies have shown that HCMV may be resistant to the induction of apoptosis by disrupting cellular pathways in glioblastoma. To investigate the potential anti-apoptotic function of HCMV in glioma, malignant U87 glioma cells were infected with HCMV. The present study showed that HCMV infection suppressed apoptosis in glioblastoma U87 cells by regulating the expression of ATF5. Furthermore, in glioblastoma U87 cells, HCMV infection induced cellular proliferation in parallel with an increase in the expression level of ATF5 and B-cell lymphoma/leukemia-2 to Bcl-2-associated X protein ratio. Loss of ATF5 function was achieved using a dominant-negative form of ATF5 in U87 cells, whereby cells appeared to grow marginally following HCMV infection when compared with the control. However, the anti-apoptotic ability was appeared to decline in the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay. These results indicate that ATF5 signaling pathways may be important in the anti-apoptotic activity of HCMV-infected glioblastoma cells; therefore, the anti-apoptotic molecular mechanisms of HCMV in human glioblastoma cells were investigated in the current study. Prevention of HCMV infection may present a potential and promising approach for the treatment of malignant gliomas. PMID:25120656

Indocyanine green videoangiography (ICGV)-guided surgery of parasagittal meningiomas occluding the superior sagittal sinus (SSS).

PubMed

d'Avella, Elena; Volpin, Francesco; Manara, Renzo; Scienza, Renato; Della Puppa, Alessandro

2013-03-01

Maximal safe resection is the goal of correct surgical treatment of parasagittal meningiomas, and it is intimately related to the venous anatomy both near and directly involved by the tumor. Indocyanine green videoangiography (ICGV) has already been advocated as an intra-operative resourceful technique in brain tumor surgery for the identification of vessels. The aim of this study was to investigate the role of ICGV in surgery of parasagittal meningiomas occluding the superior sagittal sinus (SSS). In this study, we prospectively analyzed clinical, radiological and intra-operative findings of patients affected by parasagittal meningioma occluding the SSS, who underwent ICGV assisted-surgery. Radiological diagnosis of complete SSS occlusion was pre-operatively established in all cases. ICGV was performed before dural opening, before and during tumor resection, at the end of the procedure. Five patients were included in our study. In all cases, ICGV guided dural opening, tumor resection, and venous management. The venous collateral pathway was easily identified and preserved in all cases. Radical resection was achieved in four cases. Surgery was uneventful in all cases. Despite the small number of patients, our study shows that ICG videoangiography could play a crucial role in guiding surgery of parasagittal meningioma occluding the SSS. Further studies are needed to define the role of this technique on functional and oncological outcome of these patients.

Complex Frontal Pneumosinus Dilatans Associated with Meningioma: A Report of Two Cases and Associated Literature Review.

PubMed

Timms, Sara; Lakhani, Raj; Connor, Steve; Hopkins, Claire

2017-07-01

Introduction  Pneumosinus dilatans (PSD) is a rare phenomenon involving the expansion of the paranasal sinuses, without bony destruction or a mass. Previously documented cases have demonstrated simple expansion of a solitary air cell. We present two unique cases of PSD in the presence of meningioma, in which complex new cells developed within the frontal sinus. One of the two patients developed associated sinus disease. Case 1  A 28-year-old man presented with facial pain. A computed tomography scan showed an abnormally enlarged, septated right frontal sinus, not present on childhood scans. He underwent a modified endoscopic Lothrop approach to divide the septations, and his symptoms resolved. Case 2  A 72-year-old woman presented with a 3-month history of headaches. Scans revealed a left frontal meningioma and multiple enlarged, dilated left frontal air cells. She had no clinical sinusitis and therefore was managed conservatively. Conclusions  PSD has been widely documented in association with fibrous dysplasia and meningioma. The most prevalent theory of the mechanism of PSD is of obstruction of the sinus ostium causing sinus expansion through a "ball-valve" effect. Our cases, which demonstrate septated PSD, suggest a more complex process involving local mediators and highlight the need to consider underlying meningioma in pneumosinus dilatans.

Role of human papillomavirus and its detection in potentially malignant and malignant head and neck lesions: updated review.

PubMed

Chaudhary, Ajay Kumar; Singh, Mamta; Sundaram, Shanthy; Mehrotra, Ravi

2009-06-25

Head and neck malignancies are characterized by a multiphasic and multifactorial etiopathogenesis. Tobacco and alcohol consumption are the most common risk factors for head and neck malignancy. Other factors, including DNA viruses, especially human papilloma virus (HPV), may also play a role in the initiation or development of these lesions. The pathways of HPV transmission in the head and neck mucosal lesions include oral-genital contact, more than one sexual partner and perinatal transmission of HPV to the neonatal child. The increase in prevalence of HPV infection in these lesions may be due to wider acceptance of oral sex among teenagers and adults as this is perceived to be a form of safe sex. The prevalence of HPV in benign lesions as well as malignancies has been assessed by many techniques. Among these, the polymerase chain reaction is the most sensitive method. Review of literature reveals that HPV may be a risk factor for malignancies, but not in all cases. For confirmation of the role of HPV in head and neck squamous cell carcinoma, large population studies are necessary in an assortment of clinical settings. Prophylactic vaccination against high-risk HPV types eventually may prevent a significant number of cervical carcinomas. Of the two vaccines currently available, Gardasil (Merck & Co., Inc.) protects against HPV types 6, 11, 16 and 18, while the other vaccine, Cervarix (GlaxoSmithKline, Rixensart, Belgium) protects against HPV types 16 and 18 only. However, the HPV vaccine has, to the best of our knowledge, not been tried in head and neck carcinoma. The role of HPV in etiopathogenesis, prevalence in benign and malignant lesions of this area and vaccination strategies are briefly reviewed here.

Occupational exposure to metals and risk of meningioma: a multinational case-control study.

PubMed

Sadetzki, Siegal; Chetrit, Angela; Turner, Michelle C; van Tongeren, Martie; Benke, Geza; Figuerola, Jordi; Fleming, Sarah; Hours, Martine; Kincl, Laurel; Krewski, Daniel; McLean, Dave; Parent, Marie-Elise; Richardson, Lesley; Schlehofer, Brigitte; Schlaefer, Klaus; Blettner, Maria; Schüz, Joachim; Siemiatycki, Jack; Cardis, Elisabeth

2016-12-01

The aim of the study was to examine associations between occupational exposure to metals and meningioma risk in the international INTEROCC study. INTEROCC is a seven-country population-based case-control study including 1906 adult meningioma cases and 5565 population controls. Incident cases were recruited between 2000 and 2004. A detailed occupational history was completed and job titles were coded into standard international occupational classifications. Estimates of mean workday exposure to individual metals and to welding fumes were assigned based on a job-exposure-matrix. Adjusted odds ratios (ORs) and 95 % confidence intervals (CIs) were estimated using conditional logistic regression. Although more controls than cases were ever exposed to metals (14 vs. 11 %, respectively), cases had higher median cumulative exposure levels. The ORs for ever vs. never exposure to any metal and to individual metals were mostly greater than 1.0, with the strongest association for exposure to iron (OR 1.26, 95 % CI 1.0-1.58). In women, an increased OR of 1.70 (95 % CI 1.0-2.89) was seen for ever vs never exposure to iron (OR in men 1.19, 95 % CI 0.91-1.54), with positive trends in relation with both cumulative and duration of exposure. These results remained after consideration of other occupational metal or chemical co-exposures. In conclusion, an apparent positive association between occupational exposure to iron and meningioma risk was observed, particularly among women. Considering the fact that meningioma is a hormone dependent tumor, the hypothesis that an interaction between iron and estrogen metabolism may be a potential mechanism for a carcinogenic effect of iron should be further investigated.

Physiological serum copper concentrations found in malignancies cause unfolding induced aggregation of human serum albumin in vitro.

PubMed

Rizvi, Asim; Furkan, Mohd; Naseem, Imrana

2017-12-15

Malignancies are characterized by several drastic metabolic changes, one of which is a progressive rise in the levels of serum copper. This rise in serum copper is documented across all malignancies and across malignancies in several species. This study aims to explore in vitro the effect of increased copper levels on the structure of the blood protein human serum albumin. Exposure of human serum albumin to physiologically relevant copper concentrations for 21 days resulted in structural modifications in the protein which were evident by changes in the intrinsic florescence. A loss of the predominantly alpha helical structure of human serum albumin was recorded along with a tendency to form protein aggregates. This aggregation was characterized by Thioflavin T and Congo Red assays. Rayleigh light scattering and turbidity assays confirmed aggregation. The aggregates were visually confirmed using transmission electron microscopy. This is the first report implicating increased copper levels as a cause of aggregation of blood proteins in malignancies. The physiological and biochemical implications of this phenomenon are discussed. Copyright © 2017. Published by Elsevier Inc.

Combination of Vaccine-Strain Measles and Mumps Viruses Enhances Oncolytic Activity against Human Solid Malignancies.

PubMed

Son, Ho Anh; Zhang, LiFeng; Cuong, Bui Khac; Van Tong, Hoang; Cuong, Le Duy; Hang, Ngo Thu; Nhung, Hoang Thi My; Yamamoto, Naoki; Toan, Nguyen Linh

2018-02-07

Oncolytic measles and mumps viruses (MeV, MuV) have a potential for anti-cancer treatment. We examined the anti-tumor activity of MeV, MuV, and MeV-MuV combination (MM) against human solid malignancies (HSM). MeV, MuV, and MM targeted and significantly killed various cancer cell lines of HSM but not normal cells. MM demonstrated a greater anti-tumor effect and prolonged survival in a human prostate cancer xenograft tumor model compared to MeV and MuV. MeV, MuV, and MM significantly induced the expression of immunogenic cell death markers and enhanced spleen-infiltrating immune cells. In conclusion, MM combination significantly improves the treatment of human solid malignancies.

Comparative gene expression profiling of ADAMs, MMPs, TIMPs, EMMPRIN, EGF-R and VEGFA in low grade meningioma.

PubMed

Rooprai, Harcharan K; Martin, Andrew J; King, Andrew; Appadu, Usha D; Jones, Huw; Selway, Richard P; Gullan, Richard W; Pilkington, Geoffrey J

2016-12-01

MMPs (matrix metalloproteinases), ADAMs (a disintegrin and metalloproteinase) and TIMPs (tissue inhibitors of metalloproteinases) are implicated in invasion and angiogenesis: both are tissue remodeling processes involving regulated proteolysis of the extracellular matrix, growth factors and their receptors. The expression of these three groups and their correlations with clinical behaviour has been reported in gliomas but a similar comprehensive study in meningiomas is lacking. In this study, we aimed to evaluate the patterns of expression of 23 MMPs, 4 TIMPs, 8 ADAMs, selective growth factors and their receptors in 17 benign meningiomas using a quantitative real-time polymerase chain reaction (qPCR). Results indicated very high gene expression of 13 proteases, inhibitors and growth factors studied: MMP2 and MMP14, TIMP-1, -2 and -3, ADAM9, 10, 12, 15 and 17, EGF-R, EMMPRIN and VEGF-A, in almost every meningioma. Expression pattern analysis showed several positive correlations between MMPs, ADAMs, TIMPs and growth factors. Furthermore, our findings suggest that expression of MMP14, ADAM9, 10, 12, 15 and 17, TIMP-2, EGF-R and EMMPRIN reflects histological subtype of meningioma such that fibroblastic subtype had the highest mRNA expression, transitional subtype was intermediate and meningothelial type had the lowest expression. In conclusion, this is the first comprehensive study characterizing gene expression of 8 ADAMs in meningiomas. These neoplasms, although by histological definition benign, have invasive potential. Taken together, the selected elevated gene expression pattern may serve to identify targets for therapeutic intervention or indicators of biological progression and recurrence.

Fractionated stereotactic radiotherapy in patients with benign or atypical intracranial meningioma: Long-term experience and prognostic factors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Milker-Zabel, Stefanie; Zabel, Angelika; Schulz-Ertner, Daniela

Purpose: To analyze our long-term experience and prognostic factors after fractionated stereotactic radiotherapy (FSRT) in patients with benign or atypical intracranial meningioma. Methods and materials: Between January 1985 and December 2001, 317 patients with a median age of 55.7 years were treated with FSRT for intracranial meningioma. The tumor distribution was World Health Organization (WHO) Grade 1 in 48.3%, WHO Grade 2 in 8.2%, and unknown in 43.5%. Of the 317 patients, 97 underwent RT as their primary treatment, 79 underwent postoperative RT (subtotal resection in 38 and biopsy only in 41), and 141 were treated for recurrent disease. Themore » median target volume was 33.6 cm{sup 3} (range, 1.0-412.6 cm{sup 3}). The median total dose was 57.6 Gy at 1.8 Gy/fraction five times weekly. Results: The median follow-up was 5.7 years (range, 1.2-14.3 years). The overall local tumor control rate was 93.1% (295 of 317). Of the 317 patients, 72 had a partial response on CT/MRI and 223 (70.4%) remained stable. At a median of 4.5 years after FSRT, 22 patients (6.9%) had local tumor progression on MRI. Local tumor failure was significantly greater in patients with WHO Grade 2 meningioma (p < 0.002) than in patients with WHO Grade 1 or unknown histologic features. Patients treated for recurrent meningioma showed a trend toward decreased progression-free survival compared with patients treated with primary therapy, after biopsy, or after subtotal resection (p < 0.06). Patients with a tumor volume >60 cm{sup 3} had a recurrence rate of 15.5% vs. 4.3% for those with a tumor volume of {<=}60 cm{sup 3} (p < 0.001). In 42.9% of the patients, preexisting neurologic deficits improved. Worsening of preexisting neurologic symptoms occurred in 8.2%. Eight patients developed new clinical symptoms, such as reduced vision, trigeminal neuralgia, and intermittent tinnitus located at the side of the irradiated meningioma after FSRT. Conclusion: These data have demonstrated that FSRT is

'Decoy' and 'non-decoy' functions of DcR3 promote malignant potential in human malignant fibrous histiocytoma cells.

PubMed

Toda, Mitsunori; Kawamoto, Teruya; Ueha, Takeshi; Kishimoto, Kenta; Hara, Hitomi; Fukase, Naomasa; Onishi, Yasuo; Harada, Risa; Minoda, Masaya; Kurosaka, Masahiro; Akisue, Toshihiro

2013-09-01

Decoy receptor 3 (DcR3) is a soluble secreted protein that belongs to the tumor necrosis factor receptor (TNFR) superfamily. DcR3 inhibits the Fas ligand (FasL)/Fas apoptotic pathway by binding to FasL, competitively with Fas receptor. Previous studies have reported that overexpression of DcR3 has been detected in various human malignancies and that DcR3 functions as a 'decoy' for FasL to inhibit FasL-induced apoptosis. In addition, recent studies have revealed that DcR3 has 'non-decoy' functions to promote tumor cell migration and invasion, suggesting that DcR3 may play important roles in tumor progression by decoy and non-decoy functions. We have previously reported that overexpression of DcR3 was observed in human malignant fibrous histiocytoma (MFH), however, the roles of DcR3 in MFH have not been studied. In the present study, to elucidate the roles of DcR3 in tumor progression of MFH, we examined the effects of DcR3 inhibition on cell apoptosis, migration and invasion in human MFH cells. siRNA knockdown of DcR3 enhanced the FasL-induced apoptotic activity and significantly decreased cell migration and invasion with a decrease in the activation of phosphatidylinositol 3 kinase (PI3K)/Akt and matrix metalloproteinase (MMP)-2. The findings in this study strongly suggest that DcR3 plays important roles in tumor progression of human MFH by decoy as well as non-decoy functions and that DcR3 may serve as a potent therapeutic target for human MFH.

Use of Sodium Fluorescein in Meningioma Surgery Performed Under the YELLOW-560 nm Surgical Microscope Filter: Feasibility and Preliminary Results.

PubMed

Akçakaya, Mehmet Osman; Göker, Burcu; Kasımcan, Mustafa Ömür; Hamamcıoğlu, Mustafa Kemal; Kırış, Talat

2017-11-01

To evaluate the feasibility of sodium fluorescein (Na-Fl)-guided surgery involving the use of the PENTERO 900 surgical microscope equipped with the YELLOW-560 nm filter and low-dose Na-FL (200 mg/2-4 mg/kg) in meningioma surgery. The study included 30 patients with newly diagnosed or recurrent meningiomas who underwent Na-Fl-guided surgery between April 2015 and December 2016. Clinical features, surgical observations, extent of resection, and tumor histopathology were retrospectively analyzed. The Na-Fl enhancement pattern was assessed as "no enhancement," "diffuse homogenous enhancement," or "low heterogeneous enhancement." There were 30 meningiomas among the 30 patients. In 25 patients, Na-Fl was used for tumor demarcation, whereas in 5 patients, it was used for videoangiography. In this series, 88% of tumors showed diffuse homogeneous Na-Fl enhancement during the operation. The resection rate of the meningiomas was 87%. In 5 patients, in whom Na-Fl was used for videoangiography, the approach was useful to evaluate Na-Fl-stained vessels for patency and to understand their relationship with the tumor. No adverse events were encountered with regard to Na-Fl use. Na-Fl guidance with the use of the YELLOW-560 filter is safe and effective during meningioma surgery. Copyright © 2017 Elsevier Inc. All rights reserved.

Histopathology of radiation necrosis with severe peritumoral edema after gamma knife radiosurgery for parasagittal meningioma. A report of two cases.

PubMed

Chen, Chien-hua; Shen, Chiung-chyi; Sun, Ming-hsi; Ho, William L; Huang, Chuan-fu; Kwan, Po-cheung

2007-01-01

Gamma knife radiosurgery (GKS) has been an effective treatment for meningiomas. Nevertheless, it still has certain risks. We present 2 cases of parasagittal meningioma after GKS complicated with radiation necrosis and peritumoral edema. The results of histologic examination are discussed. Two cases of parasagittal meningioma received GKS. Symptomatic peritumoral edema developed 3-4 months after GKS. Both of them underwent surgical resection of their tumor afterwards. Histologic examination showed necrotic change inside the tumor and infiltration of inflammatory cells in both cases. Hyalinization of blood vessels was seen in the 2nd case. The patients had improvement of neurologic function after surgical resection. Imaging performed 3 months after surgical resection showed alleviation of brain edema. After radiosurgery peritumoral edema tends to occur in meningiomas with a parasagittal position. Radiation necrosis, infiltration of inflammatory cells, and radiation injury to the vasculature causing hyalinization of blood vessels are suggested as the underlying histopathology. (c) 2007 S. Karger AG, Basel.

Combined cord blood and bone marrow transplantation from the same human leucocyte antigen-identical sibling donor for children with malignant and non-malignant diseases.

PubMed

Tucunduva, Luciana; Volt, Fernanda; Cunha, Renato; Locatelli, Franco; Zecca, Marco; Yesilipek, Akif; Caniglia, Maurizio; Güngör, Tayfun; Aksoylar, Serap; Fagioli, Franca; Bertrand, Yves; Addari, Maria Carmen; de la Fuente, Josu; Winiarski, Jacek; Biondi, Andrea; Sengeloev, Henrik; Badell, Isabel; Mellgren, Karin; de Heredia, Cristina Díaz; Sedlacek, Petr; Vora, Ajay; Rocha, Vanderson; Ruggeri, Annalisa; Gluckman, Eliane

2015-04-01

Umbilical cord blood (UCB) from an human leucocyte antigen (HLA)-identical sibling can be used for transplantation of patients with malignant and non-malignant diseases. However, the low cellular content of most UCB units represents a limitation to this approach. An option to increase cell dose is to harvest bone marrow (BM) cells from the same donor and infuse them along with the UCB. We studied 156 children who received such a combined graft between 1992 and 2011. Median age was 7 years and 78% of patients (n = 122) were transplanted for non-malignant diseases, mainly haemoglobinopathies. Acute leukaemia (n = 26) was the most frequent malignant diagnosis. Most patients (91%) received myeloablative conditioning. Median donor age was 1·7 years, median infused nucleated cell dose was 24·4 × 10(7) /kg and median follow-up was 41 months. Sixty-days neutrophil recovery occurred in 96% of patients at a median of 17 d. The probabilities of grade-II-IV acute and chronic graft-versus-host disease (GVHD) were 19% and 10%, respectively. Four-year overall survival was 90% (68% malignant; 97% non-malignant diseases) with 3% probability of death. In conclusion, combined UCB and BM transplantation from an HLA-identical sibling donor is an effective treatment for children with malignant and non-malignant disorders with high overall survival and low incidence of GVHD. © 2014 John Wiley & Sons Ltd.

Intramedullary Recurrence of a Thoracic Meningioma-Presentation of an Unusual Case and Review of the Literature.

PubMed

Piazza, Matthew A; Ramayya, Ashwin G; Geiger, Geoffrey A; Alonso-Basanta, Michelle; Nasrallah, MacLean P; Welch, William C; Ozturk, Ali K

2016-08-01

Spinal meningiomas are typically extra-axial, slow-growing, benign tumors that arise from the arachnoid cap cells. Intramedullary spinal meningiomas are exceedingly rare with few cases reported in the literature. A 64-year-old man with a history of grade I thoracic meningioma at the T4 level resected initially in 1989 and who required reoperation in 2013 for intradural, extramedullary recurrence of tumor presented again in 2015 with gait difficulty. Magnetic resonance imaging revealed a soft tissue mass at the T3 to T4 levels on the left side of the canal that was mildly enhancing on T1 contrasted sequences. The patient was taken to the operating room, where a purely intramedullary recurrence was discovered without extramedullary extension or a dural-based attachment. The intramedullary tumor was completely resected, and postoperatively the patient recovered well and was at his neurologic baseline. The patient ultimately underwent proton beam radiotherapy because this tumor, although benign, had recurred twice. Intramedullary spinal meningiomas, particularly intramedullary low-grade recurrence of a previously extramedullary tumor, are rare phenomena. Although the pathogenic mechanisms are not well understood, intramedullary recurrence as described in this patient may reflect extrinsic factors related to prior surgical resections in addition to histologic progression. When operating on recurrent extramedullary lesions, aggressive arachnoid dissection may predispose patients to unusual patterns of recurrence. Copyright © 2016 Elsevier Inc. All rights reserved.

Brain invasion and the risk of seizures in patients with meningioma.

PubMed

Hess, Katharina; Spille, Dorothee Cäcilia; Adeli, Alborz; Sporns, Peter B; Brokinkel, Caroline; Grauer, Oliver; Mawrin, Christian; Stummer, Walter; Paulus, Werner; Brokinkel, Benjamin

2018-04-27

OBJECTIVE Identification of risk factors for perioperative epilepsy remains crucial in the care of patients with meningioma. Moreover, associations of brain invasion with clinical and radiological variables have been largely unexplored. The authors hypothesized that invasion of the cortex and subsequent increased edema facilitate seizures, and they compared radiological data and perioperative seizures in patients with brain-invasive or noninvasive meningioma. METHODS Correlations of brain invasion with tumor and edema volumes and preoperative and postoperative seizures were analyzed in univariate and multivariate analyses. RESULTS Totals of 108 (61%) females and 68 (39%) males with a median age of 60 years and harboring totals of 92 (52%) grade I, 79 (45%) grade II, and 5 (3%) grade III tumors were included. Brain invasion was found in 38 (22%) patients and was absent in 138 (78%) patients. The tumors were located at the convexity in 72 (41%) patients, at the falx cerebri in 26 (15%), at the skull base in 69 (39%), in the posterior fossa in 7 (4%), and in the ventricle in 2 (1%); the median tumor and edema volumes were 13.73 cm 3 (range 0.81-162.22 cm 3 ) and 1.38 cm 3 (range 0.00-355.80 cm 3 ), respectively. As expected, edema volume increased with rising tumor volume (p < 0.001). Brain invasion was independent of tumor volume (p = 0.176) but strongly correlated with edema volume (p < 0.001). The mean edema volume in noninvasive tumors was 33.0 cm 3 , but in invasive tumors, it was 130.7 cm 3 (p = 0.008). The frequency of preoperative seizures was independent of the patients' age, sex, and tumor location; however, the frequency was 32% (n = 12) in patients with invasive meningioma and 15% (n = 21) in those with noninvasive meningioma (p = 0.033). In contrast, the probability of detecting brain invasion microscopically was increased more than 2-fold in patients with a history of preoperative seizures (OR 2.57, 95% CI 1.13-5.88; p = 0.025). In univariate analyses

Three-dimensional multimodality fusion imaging as an educational and planning tool for deep-seated meningiomas.

PubMed

Sato, Mitsuru; Tateishi, Kensuke; Murata, Hidetoshi; Kin, Taichi; Suenaga, Jun; Takase, Hajime; Yoneyama, Tomohiro; Nishii, Toshiaki; Tateishi, Ukihide; Yamamoto, Tetsuya; Saito, Nobuhito; Inoue, Tomio; Kawahara, Nobutaka

2018-06-26

The utility of surgical simulation with three-dimensional multimodality fusion imaging (3D-MFI) has been demonstrated. However, its potential in deep-seated brain lesions remains unknown. The aim of this study was to investigate the impact of 3D-MFI in deep-seated meningioma operations. Fourteen patients with deeply located meningiomas were included in this study. We constructed 3D-MFIs by fusing high-resolution magnetic resonance (MR) and computed tomography (CT) images with a rotational digital subtraction angiogram (DSA) in all patients. The surgical procedure was simulated by 3D-MFI prior to operation. To assess the impact on neurosurgical education, the objective values of surgical simulation by 3D-MFIs/virtual reality (VR) video were evaluated. To validate the quality of 3D-MFIs, intraoperative findings were compared. The identification rate (IR) and positive predictive value (PPV) for the tumor feeding arteries and involved perforating arteries and veins were also assessed for quality assessment of 3D-MFI. After surgical simulation by 3D-MFIs, near-total resection was achieved in 13 of 14 (92.9%) patients without neurological complications. 3D-MFIs significantly contributed to the understanding of surgical anatomy and optimal surgical view (p < .0001) and learning how to preserve critical vessels (p < .0001) and resect tumors safety and extensively (p < .0001) by neurosurgical residents/fellows. The IR of 3D-MFI for tumor-feeding arteries and perforating arteries and veins was 100% and 92.9%, respectively. The PPV of 3D-MFI for tumor-feeding arteries and perforating arteries and veins was 98.8% and 76.5%, respectively. 3D-MFI contributed to learn skull base meningioma surgery. Also, 3D-MFI provided high quality to identify critical anatomical structures within or adjacent to deep-seated meningiomas. Thus, 3D-MFI is promising educational and surgical planning tool for meningiomas in deep-seated regions.

Diagnosis of human malignancies using laser-induced breakdown spectroscopy in combination with chemometric methods

NASA Astrophysics Data System (ADS)

Chen, Xue; Li, Xiaohui; Yu, Xin; Chen, Deying; Liu, Aichun

2018-01-01

Diagnosis of malignancies is a challenging clinical issue. In this work, we present quick and robust diagnosis and discrimination of lymphoma and multiple myeloma (MM) using laser-induced breakdown spectroscopy (LIBS) conducted on human serum samples, in combination with chemometric methods. The serum samples collected from lymphoma and MM cancer patients and healthy controls were deposited on filter papers and ablated with a pulsed 1064 nm Nd:YAG laser. 24 atomic lines of Ca, Na, K, H, O, and N were selected for malignancy diagnosis. Principal component analysis (PCA), linear discriminant analysis (LDA), quadratic discriminant analysis (QDA), and k nearest neighbors (kNN) classification were applied to build the malignancy diagnosis and discrimination models. The performances of the models were evaluated using 10-fold cross validation. The discrimination accuracy, confusion matrix and receiver operating characteristic (ROC) curves were obtained. The values of area under the ROC curve (AUC), sensitivity and specificity at the cut-points were determined. The kNN model exhibits the best performances with overall discrimination accuracy of 96.0%. Distinct discrimination between malignancies and healthy controls has been achieved with AUC, sensitivity and specificity for healthy controls all approaching 1. For lymphoma, the best discrimination performance values are AUC = 0.990, sensitivity = 0.970 and specificity = 0.956. For MM, the corresponding values are AUC = 0.986, sensitivity = 0.892 and specificity = 0.994. The results show that the serum-LIBS technique can serve as a quick, less invasive and robust method for diagnosis and discrimination of human malignancies.

Proposal for a new risk stratification classification for meningioma based on patient age, WHO tumor grade, size, localization, and karyotype

PubMed Central

Domingues, Patrícia Henriques; Sousa, Pablo; Otero, Álvaro; Gonçalves, Jesus Maria; Ruiz, Laura; de Oliveira, Catarina; Lopes, Maria Celeste; Orfao, Alberto; Tabernero, Maria Dolores

2014-01-01

Background Tumor recurrence remains the major clinical complication of meningiomas, the majority of recurrences occurring among WHO grade I/benign tumors. In the present study, we propose a new scoring system for the prognostic stratification of meningioma patients based on analysis of a large series of meningiomas followed for a median of >5 years. Methods Tumor cytogenetics were systematically investigated by interphase fluorescence in situ hybridization in 302 meningioma samples, and the proposed classification was further validated in an independent series of cases (n = 132) analyzed by high-density (500K) single-nucleotide polymorphism (SNP) arrays. Results Overall, we found an adverse impact on patient relapse-free survival (RFS) for males, presence of brain edema, younger patients (<55 years), tumor size >50 mm, tumor localization at intraventricular and anterior cranial base areas, WHO grade II/III meningiomas, and complex karyotypes; the latter 5 variables showed an independent predictive value in multivariate analysis. Based on these parameters, a prognostic score was established for each individual case, and patients were stratified into 4 risk categories with significantly different (P < .001) outcomes. These included a good prognosis group, consisting of approximately 20% of cases, that showed a RFS of 100% ± 0% at 10 years and a very poor-prognosis group with a RFS rate of 0% ± 0% at 10 years. The prognostic impact of the scoring system proposed here was also retained when WHO grade I cases were considered separately (P < .001). Conclusions Based on this risk-stratification classification, different strategies may be adopted for follow-up, and eventually also for treatment, of meningioma patients at different risks for relapse. PMID:24536048

Impact of operative length on post-operative complications in meningioma surgery: a NSQIP analysis.

PubMed

Karhade, Aditya V; Fandino, Luis; Gupta, Saksham; Cote, David J; Iorgulescu, Julian B; Broekman, Marike L; Aglio, Linda S; Dunn, Ian F; Smith, Timothy R

2017-01-01

Many studies have implicated operative length as a predictor of post-operative complications, including venous thromboembolism [deep vein thrombosis (DVT) and pulmonary embolism (PE)]. We analyzed the American College of Surgeons (ACS) National Surgical Quality Improvement Program (NSQIP) database from 2006 to 2014, to evaluate whether length of operation had a statistically significant effect on post-operative complications in patients undergoing surgical resection of meningioma. Patients were included for this study if they had a post-operative diagnosis of meningioma. Patient demographics, pre-operative comorbidities, and post-operative 30-day complications were analyzed. Of 3743 patients undergoing craniotomy for meningioma, 13.6 % experienced any complication. The most common complications and their median time to occurrence were urinary tract infection (2.6 %) at 10 days postoperatively (IQR 7-15), unplanned intubation (2.5 %) at 3 days (IQR 1-7), failure to wean from ventilator (2.4 %) at 2.0 days (IQR 2-4), and DVT (2.4 %) at 6 days (IQR 11-19). Postoperatively, 3.6 % developed VTE; 2.4 % developed DVT and 1.7 % developed PE. Multivariable analysis identified older age (third and upper quartile), obesity, preoperative ventilator dependence, preoperative steroid use, anemia, and longer operative time as significant risk factors for VTE. Separate multivariable logistic regression models demonstrated longer operative time as a significant risk factor for VTE, all complications, major complications, and minor complications. Meningioma resection is associated with various post-operative complications that increase patient morbidity and mortality risk. this large, multi-institutional patient sample, longer operative length was associated with increased risk for postoperative venous thromboembolisms, as well as major and minor complications.

Surgical management of giant sphenoid wing meningiomas encasing major cerebral arteries.

PubMed

Champagne, Pierre-Olivier; Lemoine, Emile; Bojanowski, Michel W

2018-04-01

OBJECTIVE Sphenoid wing meningiomas are a heterogeneous group of tumors with variable surgical risks and prognosis. Those that have grown to a very large size, encasing the major cerebral arteries, are associated with a high risk of stroke. In reviewing the authors' series of giant sphenoid wing meningiomas, the goal was to evaluate how the extent of the tumor's invasion of surrounding structures affected the ability to safely remove the tumor and restore function. METHODS The authors conducted a retrospective study of a series of giant sphenoid wing meningiomas operated on between 1996 and 2016. Inclusion criteria were meningiomas with a globoid component ≥ 6 cm, encasing at least 1 major intradural cerebral artery. Extent of resection was measured according to Simpson grade. RESULTS This series included 12 patients, with a mean age of 59 years. Visual symptoms were the most common clinical presentation. There was complete or partial encasement of all 3 major cerebral arteries except for 3 cases in which only the anterior cerebral artery was not involved. The lateral wall of the cavernous sinus was invaded in 8 cases (67%) and the optic canal in 6 (50%). Complete resection was achieved in 2 cases (Simpson grades 2 and 3). In the remaining 10 cases of partial resection (Simpson grade 4), radical removal (> 90%) was achieved in 7 cases (70%). In the immediate postoperative period, there were no deaths. Four of 9 patients with visual deficits improved, while the 5 others remained unchanged. Two patients experienced transient neurological deficits. Other than an asymptomatic lacuna of the internal capsule, there were no ischemic lesions following surgery. Tumor recurrence occurred in 5 patients, between 24 and 168 months (mean 61 months) following surgery. CONCLUSIONS Although these giant lesions encasing major cerebral arteries are particularly treacherous for surgery, this series demonstrates that it is possible to safely achieve radical removal and at times even

Serum sialyltransferase and liver catalase activity in cachectic nude mice bearing a human malignant melanoma.

PubMed

Kondo, Y; Sato, K; Ueyama, Y; Ohsawa, N

1981-07-01

Cachexia is rare in nude mice bearing human malignant tumors even when the transplanted tumors become as large as the body size of the host. In our series on heterotransplantation of a variety of human malignant tumors into nude mice, a malignant melanoma (SEKI) was found to induce severe body weight loss in the host at the early stage of transplantation. There was no electrolyte disturbance, hyper- or hypoadrenocorticism, hyperthyroidism, or destruction of cells of vital organs to account for the weight loss. Moreover, no evidence was obtained for concomitant infection with bacteria, Mycoplasma or fungi. These cachectic mice revealed remarkably increased levels of serum sialyltransferase and decreased liver catalase activity. The removal of tumor tissues from these mice resulted in prompt recovery of body weight, serum sialyltransferase, and liver catalase activity within 1 to 2 weeks. On the basis of the results obtained, the SEKI melanoma was thought to have produced a pathophysiological state in host nude mice which was very similar to that of cachexia in cancer patients. Nude mice bearing transplants of SEKI melanoma may provide a useful system for the study of cancer cachexia in humans.

Management of Foramen Magnum Meningioma During Pregnancy: Literature Review and Case Report.

PubMed

Casabella, Amanda M; Urakov, Timur M; Basil, Gregory; Morcos, Jacques J

2017-01-01

Foramen magnum meningiomas are very rare and challenging lesions. Their presentation in women during pregnancy tremendously complicates the course of gestation. Conservative management is always the first option, but in cases of a deteriorating clinical picture, there are currently no clear guidelines on best management. A woman presents in the 30th week of pregnancy with pain and progressive numbness in right posterior aspect of neck and right arm. Foramen magnum meningioma was diagnosed and successful surgical resection was performed with intraoperative fetal hearth monitoring and three fourths prone position of the patient. We believe a three fourths prone position of a pregnant patient is safe and adequate for the far-lateral exposure of craniocervical lesions. Rapid growing of tumor can be precipitated by steroids management during pregnancy. Published by Elsevier Inc.

Olfactory Groove Meningiomas: Comparison of Extent of Frontal Lobe Changes After Lateral and Bifrontal Approaches.

PubMed

Nanda, Anil; Maiti, Tanmoy K; Bir, Shyamal C; Konar, Subhas K; Guthikonda, Bharat

2016-10-01

Olfactory groove meningiomas often are behaviorally silent. Numerous surgical approaches have been described in the literature for the successful removal of these meningiomas. Lateral (pterional/frontolateral) and anterior (bifrontal/fronto-orbito-basal) approaches with their various modifications remain the 2 major corridors in resecting them. In this study, we discuss our experience in microsurgical treatment of these tumors at our institution and assess the extent of frontal lobe damage after the resection of tumor. We reviewed the medical records of patients who underwent surgical excision of olfactory groove meningiomas from 1990 to 2014. To measure the extent of frontal lobe damage via lateral and anterior approaches, we measured the volume of porencephalic cave in the postoperative magnetic resonance imaging by using Brainlab software. The ratio of volume of porencephalic cave to tumor was measured between 2 sides and 2 approaches. Fifty-seven patients with olfactory groove meningiomas, who underwent 62 microsurgical resection procedures in 1990-2014 were included in the study (74% were more than 5 cm at presentation). Pterional and bifrontal craniotomies were the most commonly used approaches. At follow-up, the volume of porencephalic cave after lateral approach was significantly less in the side contralateral to craniotomy irrespective of tumor size. The difference between ratio of volume of porencephalic cave and initial tumor was significantly less after lateral approaches, when compared to anterior approaches. Lateral approaches (pterional/frontolateral) resulted in less frontal lobe change and better olfactory preservation in comparison to anterior approaches in present series. Published by Elsevier Inc.

Proposal of a new radiological classification system for spinal meningiomas as a descriptive tool and surgical guide.

PubMed

Bayoumi, Ahmed B; Laviv, Yosef; Yokus, Burhan; Efe, Ibrahim E; Toktas, Zafer Orkun; Kilic, Turker; Demir, Mustafa K; Konya, Deniz; Kasper, Ekkehard M

2017-11-01

1) To provide neurosurgeons and radiologists with a new quantitative and anatomical method to describe spinal meningiomas (SM) consistently. 2) To provide a guide to the surgical approach needed and amount of bony resection required based on the proposed classification. 3) To report the distribution of our 58 cases of SM over different Stages and Subtypes in correlation to the surgical treatment needed for each case. 4) To briefly review the literature on the rare non-conventional surgical corridors to resect SM. We reviewed the literature to report on previously published cohorts and classifications used to describe the location of the tumor inside the spinal canal. We reviewed the cases that were published prior showing non-conventional surgical approaches to resect spinal meningiomas. We proposed our classification system composed of Staging based on maximal cross-sectional surface area of tumor inside canal, Typing based on number of quadrants occupied by tumor and Subtyping based on location of the tumor bulk to spinal cord. Extradural and extra-spinal growth were also covered by our classification. We then applied it retrospectively on our 58 cases. 12 articles were published illustrating overlapping terms to describe spinal meningiomas. Another 7 articles were published reporting on 23 cases of anteriorly located spinal meningiomas treated with approaches other than laminectomies/laminoplasties. 4 Types, 9 Subtypes and 4 Stages were described in our Classification System. In our series of 58 patients, no midline anterior type was represented. Therefore, all our cases were treated by laminectomies or laminoplasties (with/without facetectomies) except a case with a paraspinal component where a costotransversectomy was needed. Spinal meningiomas can be radiologically described in a precise fashion. Selection of surgical corridor depends mainly on location of tumor bulk inside canal. Copyright © 2017 Elsevier B.V. All rights reserved.

Combination of peptide receptor radionuclide therapy with fractionated external beam radiotherapy for treatment of advanced symptomatic meningioma

PubMed Central

2012-01-01

Background External beam radiotherapy (EBRT) is the treatment of choice for irresectable meningioma. Due to the strong expression of somatostatin receptors, peptide receptor radionuclide therapy (PRRT) has been used in advanced cases. We assessed the feasibility and tolerability of a combination of both treatment modalities in advanced symptomatic meningioma. Methods 10 patients with irresectable meningioma were treated with PRRT (177Lu-DOTA0,Tyr3 octreotate or - DOTA0,Tyr3 octreotide) followed by external beam radiotherapy (EBRT). EBRT performed after PRRT was continued over 5–6 weeks in IMRT technique (median dose: 53.0 Gy). All patients were assessed morphologically and by positron emission tomography (PET) before therapy and were restaged after 3–6 months. Side effects were evaluated according to CTCAE 4.0. Results Median tumor dose achieved by PRRT was 7.2 Gy. During PRRT and EBRT, no side effects > CTCAE grade 2 were noted. All patients reported stabilization or improvement of tumor-associated symptoms, no morphologic tumor progression was observed in MR-imaging (median follow-up: 13.4 months). The median pre-therapeutic SUVmax in the meningiomas was 14.2 (range: 4.3–68.7). All patients with a second PET after combined PRRT + EBRT showed an increase in SUVmax (median: 37%; range: 15%–46%) to a median value of 23.7 (range: 8.0–119.0; 7 patients) while PET-estimated volume generally decreased to 81 ± 21% of the initial volume. Conclusions The combination of PRRT and EBRT is feasible and well tolerated. This approach represents an attractive strategy for the treatment of recurring or progressive symptomatic meningioma, which should be further evaluated. PMID:22720902

Different meningitis-causing bacteria induce distinct inflammatory responses on interaction with cells of the human meninges.

PubMed

Fowler, Mark I; Weller, Roy O; Heckels, John E; Christodoulides, Myron

2004-06-01

The interactions of bacterial pathogens with cells of the human leptomeninges are critical events in the progression of meningitis. An in vitro model based on the culture of human meningioma cells was used to investigate the interactions of the meningeal pathogens Escherichia coli K1, Haemophilus influenzae, Neisseria meningitidis and Streptococcus pneumoniae. A rank order of association with meningioma cells was observed, with N. meningitidis showing the highest levels of adherence, followed by E. coli, S. pneumoniae and H. influenzae. Neisseria meningitidis and H. influenzae did not invade meningioma cells or induce cell death, but induced a concentration-dependent secretion of inflammatory mediators. Neisseria meningitidis induced higher levels of IL-6, MCP-1, RANTES and GM-CSF than H. influenzae, but there was no significant difference in the levels of IL-8 induced by both pathogens. Streptococcus pneumoniae was also unable to invade meningioma cells, but low concentrations of bacteria failed to stimulate cytokine secretion. However, higher concentrations of pneumococci led to cell death. By contrast, only E. coli K1 invaded meningioma cells directly and induced rapid cell death before an inflammatory response could be induced. These data demonstrate that the interactions of different bacterial pathogens with human meningeal cells are distinct, and suggest that different intervention strategies may be needed in order to prevent the morbidity and mortality associated with bacterial meningitis.

Deficiency of the protein-tyrosine phosphatase DEP-1/PTPRJ promotes matrix metalloproteinase-9 expression in meningioma cells.

PubMed

Petermann, Astrid; Stampnik, Yvonn; Cui, Yan; Morrison, Helen; Pachow, Doreen; Kliese, Nadine; Mawrin, Christian; Böhmer, Frank-D

2015-05-01

Brain-invasive growth of a subset of meningiomas is associated with less favorable prognosis. The molecular mechanisms causing invasiveness are only partially understood, however, the expression of matrix metalloproteinases (MMPs) has been identified as a contributing factor. We have previously found that loss of density enhanced phosphatase-1 (DEP-1, also designated PTPRJ), a transmembrane protein-tyrosine phosphatase, promotes meningioma cell motility and invasive growth in an orthotopic xenotransplantation model. We have now analyzed potential alterations of the expression of genes involved in motility control, caused by DEP-1 loss in meningioma cell lines. DEP-1 depleted cells exhibited increased expression of mRNA encoding MMP-9, and the growth factors EGF and FGF-2. The increase of MMP-9 expression in DEP-1 depleted cells was also readily detectable at the protein level by zymography. MMP-9 upregulation was sensitive to chemical inhibitors of growth factor signal transduction. Conversely, MMP-9 mRNA levels could be stimulated with growth factors (e.g. EGF) and inflammatory cytokines (e.g. TNFα). Increase of MMP-9 expression by DEP-1 depletion, or growth factor/cytokine stimulation qualitatively correlated with increased invasiveness in vitro scored as transmigration through matrigel-coated membranes. The studies suggest induction of MMP-9 expression promoted by DEP-1 deficiency, or potentially by growth factors and inflammatory cytokines, as a mechanism contributing to meningioma brain invasiveness.

Schwannomatosis associated with multiple meningiomas due to a familial SMARCB1 mutation.

PubMed

Bacci, Costanza; Sestini, Roberta; Provenzano, Aldesia; Paganini, Irene; Mancini, Irene; Porfirio, Berardino; Vivarelli, Rossella; Genuardi, Maurizio; Papi, Laura

2010-02-01

Schwannomatosis (MIM 162091) is a condition predisposing to the development of central and peripheral schwannomas; most cases are sporadic without a clear family history but a few families with a clear autosomal dominant pattern of transmission have been described. Germline mutations in SMARCB1 are associated with schwannomatosis. We report a family with multiple schwannomas and meningiomas. A SMARCB1 germline mutation in exon 1 was identified. The mutation, c.92A>T (p.Glu31Val), occurs in a highly conserved amino acid in the SMARCB1 protein. In addition, in silico analysis demonstrated that the mutation disrupts the donor consensus sequence of exon 1. RNA studies verified the absence of mRNA transcribed by the mutant allele. This is the first report of a SMARCB1 germline mutation in a family with schwannomatosis characterized by the development of multiple meningiomas.

Basic and clinical aspects of malignant melanoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nathanson, L.

1987-01-01

This book contains the following 10 chapters: The role of oncogenes in the pathogenesis of malignant melanoma; Laminin and fibronectin modulate the metastatic activity of melanoma cells; Structure, function and biosynthesis of ganglioside antigens associated with human tumors derived from the neuroectoderm; Epidemiology of ocular melanoma; Malignant melanoma: Prognostic factors; Endocrine influences on the natural history of human malignant melanoma; Psychosocial factors associated with prognostic indicators, progression, psychophysiology, and tumor-host response in cutaneous malignant melanoma; Central nervous system metastases in malignant melanoma; Interferon trials in the management of malignant melanoma and other neoplasms: an overview; and The treatment of malignantmore » melanoma by fast neutrons.« less

In vitro terahertz spectroscopy of gelatin-embedded human brain tumors: a pilot study

NASA Astrophysics Data System (ADS)

Chernomyrdin, N. V.; Gavdush, A. A.; Beshplav, S.-I. T.; Malakhov, K. M.; Kucheryavenko, A. S.; Katyba, G. M.; Dolganova, I. N.; Goryaynov, S. A.; Karasik, V. E.; Spektor, I. E.; Kurlov, V. N.; Yurchenko, S. O.; Komandin, G. A.; Potapov, A. A.; Tuchin, V. V.; Zaytsev, K. I.

2018-04-01

We have performed the in vitro terahertz (THz) spectroscopy of human brain tumors. In order to fix tissues for the THz measurements, we have applied the gelatin embedding. It allows for preserving tissues from hydration/dehydration and sustaining their THz response similar to that of the freshly-excised tissues for a long time after resection. We have assembled an experimental setup for the reflection-mode measurements of human brain tissues based on the THz pulsed spectrometer. We have used this setup to study in vitro the refractive index and the amplitude absorption coefficient of 2 samples of malignant glioma (grade IV), 1 sample of meningioma (grade I), and samples of intact tissues. We have observed significant differences between the THz responses of normal and pathological tissues of the brain. The results of this paper highlight the potential of the THz technology in the intraoperative neurodiagnosis of tumors relying on the endogenous labels of tumorous tissues.

Meningioma patients diagnosed 2007-2009 and the association with use of mobile and cordless phones: a case-control study.

PubMed

Carlberg, Michael; Söderqvist, Fredrik; Hansson Mild, Kjell; Hardell, Lennart

2013-07-19

To study the association between use of wireless phones and meningioma. We performed a case-control study on brain tumour cases of both genders aged 18-75 years and diagnosed during 2007-2009. One population-based control matched on gender and age was used to each case. Here we report on meningioma cases including all available controls. Exposures were assessed by a questionnaire. Unconditional logistic regression analysis was performed. In total 709 meningioma cases and 1,368 control subjects answered the questionnaire. Mobile phone use in total produced odds ratio (OR) = 1.0, 95% confidence interval (CI) = 0.7-1.4 and cordless phone use gave OR = 1.1, 95% CI = 0.8-1.5. The risk increased statistically significant per 100 h of cumulative use and highest OR was found in the fourth quartile (>2,376 hours) of cumulative use for all studied phone types. There was no statistically significant increased risk for ipsilateral mobile or cordless phone use, for meningioma in the temporal lobe or per year of latency. Tumour volume was not related to latency or cumulative use in hours of wireless phones. No conclusive evidence of an association between use of mobile and cordless phones and meningioma was found. An indication of increased risk was seen in the group with highest cumulative use but was not supported by statistically significant increasing risk with latency. Results for even longer latency periods of wireless phone use than in this study are desirable.

Trends in Management of Intracranial Meningiomas: Analysis of 49,921 Cases from Modern Cohort.

PubMed

Agarwal, Vijay; McCutcheon, Brandon A; Hughes, Joshua D; Carlson, Matthew L; Glasgow, Amy E; Habermann, Elizabeth B; Nguyen, Quoc-Bao; Link, Michael J; Van Gompel, Jamie J

2017-10-01

We sought to characterize patterns and treatment for intracranial meningiomas in the Surveillance, Epidemiology, and End Results set of cancer registries. SEER data was queried from 2004-2012 for cases of intracranial meningioma using appropriate topography and histology codes. A total of 49,921 patients with intracranial meningioma were identified. The vast majority of cases were associated with a benign histology (n = 47,047, 94.2%). There were 21,145 patients (42.4%) who underwent surgical management, 2783 who received radiation alone (5.6%), and 25,993 who underwent surveillance only (52.1%). Surgical management decreased in frequency from 48.8% of all cases in 2004 to 38.3% of cases in 2012 (P < 0.001). Radiation alone remained stable over time with a range of 4.8%-6.3% of cases. Observation increased from 45.0% of cases in 2004 to 56.7% of cases in 2012 (P < 0.001). On unadjusted analysis, surgical management was associated with younger age and larger tumor size. The incidence of tumors <2 cm in size increased significantly over the study period from 29.7% in 2004 to 41.7% in 2012 (P < 0.001). After adjusting for tumor size, multivariable analysis demonstrated that the odds of observation as a primary management strategy were greater in 2012 relative to 2004 (odds ratio 1.33, 95% confidence interval 1.21-1.45). The incidence of intracranial meningiomas increased, while tumor size at the time of diagnosis decreased. Moreover, the number undergoing no treatment increased as a treatment strategy and was more likely employed for older patients, those of African-American race, and those with smaller tumors. Copyright © 2017 Elsevier Inc. All rights reserved.

Glycerophosphodiester phosphodiesterase domain containing 5 (GDPD5) expression correlates with malignant choline phospholipid metabolite profiles in human breast cancer

PubMed Central

Cao, Maria D.; Döpkens, Mailin; Krishnamachary, Balaji; Vesuna, Farhad; Gadiya, Mayur M.; Loenning, Per E.; Bhujwalla, Zaver M.; Gribbestad, Ingrid S.; Glunde, Kristine

2012-01-01

Altered choline phospholipid metabolism is a hallmark of cancer, leading to malignant choline metabolite profiles consisting of low glycerophosphocholine (GPC) and high phosphocholine (PC) in human breast cancers. Glycerophosphocholine phosphodiesterase (GPC-PDE) catalyzes the degradation of GPC to free choline and glycerol-3-phosphate. The gene(s) encoding for the GPC-PDE(s) responsible for GPC degradation in breast cancers have not yet been identified. Here we have demonstrated for the first time that the GPC-PDE encoded by glycerophosphodiester phosphodiesterase domain containing 5 (GDPD5) is associated with breast cancer malignancy. Two human breast cancer cell lines (n=8 and 10) and primary human breast tumor samples (n=19) were studied with combined magnetic resonance spectroscopy (MRS) and qRT-PCR to investigate several isoforms of GDPD expression with respect to choline phospholipid metabolite levels. Out of five GDPDs tested, GDPD5 was found to be significantly overexpressed in highly malignant estrogen receptor negative (ER−) compared to weakly malignant estrogen receptor positive (ER+) human breast cancer cells (P=0.027) and breast tumors from patients (P=0.015). GDPD5 showed significantly positive correlations with PC (P<0.001), total choline (tCho) (P=0.007) and PC/GPC (P<0.001) levels in human breast tumors. GDPD5 showed a trend towards negative correlation with GPC levels (P=0.130). Human breast cancers with malignant choline metabolite profiles consisting of low GPC and high PC levels highly co-expressed GDPD5, choline kinase alpha (CHKA), and phosphatidylcholine-specific phospholipase D1 (PLD1), while cancers containing high GPC and relatively low PC levels displayed low co-expression of GDPD5, CHKA, and PLD1. GDPD5, CHKA and PLD1 were significantly overexpressed in highly malignant ER− tumors in our patient cohort. Our study identified GDPD5 as a GPC-PDE that likely participates in regulating choline phospholipid metabolism in breast cancer

Meningioma-like tumor of the skin. An ultrastructural and immunohistochemical study.

PubMed

Barr, R J; Yi, E S; Jensen, J L; Wuerker, R B; Liao, S Y

1993-08-01

Three unusual cutaneous tumors are described along with ultrastructural and immunohistochemical studies. All lesions were asymptomatic red-brown papulonodules. Light microscopic examination revealed a whorled configuration of spindle-shaped cells, some concentrically arranged around blood vessels. Immunohistochemical panels exhibited positive staining only with antibody to vimentin and negative staining with antibodies against S-100 protein, muscle markers, cytokeratin, epithelial membrane antigen, Leu 7, type IV collagen, and factor XIIIa, ruling out obvious nevomelanocytic, nerve sheath, meningothelial, smooth muscle, and perithelial differentiation. Electron microscopic examination demonstrated cells producing poorly formed collagen fibrils, sparse collagen fibers, and possessing occasional ill-defined intercellular junctions between their elongated cell processes. This rare tumor is considered to be either an immature fibrohistiocytic or possibly a nerve sheath neoplasm with striking similarities to so-called canine hemangiopericytoma. Because the prominent whorled pattern was reminiscent of meningioma, the lesion was referred to as meningioma-like tumor of the skin.

[A graph cuts-based interactive method for segmentation of magnetic resonance images of meningioma].

PubMed

Li, Shuan-qiang; Feng, Qian-jin; Chen, Wu-fan; Lin, Ya-zhong

2011-06-01

For accurate segmentation of the magnetic resonance (MR) images of meningioma, we propose a novel interactive segmentation method based on graph cuts. The high dimensional image features was extracted, and for each pixel, the probabilities of its origin, either the tumor or the background regions, were estimated by exploiting the weighted K-nearest neighborhood classifier. Based on these probabilities, a new energy function was proposed. Finally, a graph cut optimal framework was used for the solution of the energy function. The proposed method was evaluated by application in the segmentation of MR images of meningioma, and the results showed that the method significantly improved the segmentation accuracy compared with the gray level information-based graph cut method.

Minimally Invasive Supraorbital Key-hole Approach for the Treatment of Anterior Cranial Fossa Meningiomas

PubMed Central

IACOANGELI, Maurizio; NOCCHI, Niccolò; NASI, Davide; DI RIENZO, Alessandro; DOBRAN, Mauro; GLADI, Maurizio; COLASANTI, Roberto; ALVARO, Lorenzo; POLONARA, Gabriele; SCERRATI, Massimo

2016-01-01

The most important target of minimally invasive surgery is to obtain the best therapeutic effect with the least iatrogenic injury. In this background, a pivotal role in contemporary neurosurgery is played by the supraorbital key-hole approach proposed by Perneczky for anterior cranial base surgery. In this article, it is presented as a possible valid alternative to the traditional craniotomies in anterior cranial fossa meningiomas removal. From January 2008 to January 2012 at our department 56 patients underwent anterior cranial base meningiomas removal. Thirty-three patients were submitted to traditional approaches while 23 to supraorbital key-hole technique. A clinical and neuroradiological pre- and postoperative evaluation were performed, with attention to eventual complications, length of surgical procedure, and hospitalization. Compared to traditional approaches the supraorbital key-hole approach was associated neither to a greater range of postoperative complications nor to a longer surgical procedure and hospitalization while permitting the same lesion control. With this technique, minimization of brain exposition and manipulation with reduction of unwanted iatrogenic injuries, neurovascular structures preservation, and a better aesthetic result are possible. The supraorbital key-hole approach according to Perneckzy could represent a valid alternative to traditional approaches in anterior cranial base meningiomas surgery. PMID:26804334

Malignant Transformation Potentials of Human Umbilical Cord Mesenchymal Stem Cells Both Spontaneously and via 3-Methycholanthrene Induction

PubMed Central

Lai, Xiulan; Liu, Sizheng; Chen, Yezeng; Zheng, Zexin; Xie, Qingdong; Maldonado, Martin; Cai, Zhiwei; Qin, Shan; Ho, Guyu; Ma, Lian

2013-01-01

Human umbilical cord mesenchymal stem cells (HUMSCs) are highly proliferative and can be induced to differentiate into advanced derivatives of all three germ layers. Thus, HUMSCs are considered to be a promising source for cell-targeted therapies and tissue engineering. However there are reports on spontaneous transformation of mesenchymal stem cells (MSCs) derived from human bone marrows. The capacity for HUMSCs to undergo malignant transform spontaneously or via induction by chemical carcinogens is presently unknown. Therefore, we isolated HUMSCs from 10 donors and assessed their transformation potential either spontaneously or by treating them with 3-methycholanthrene (3-MCA), a DNA-damaging carcinogen. The malignant transformation of HUMSCs in vitro was evaluated by morphological changes, proliferation rates, ability to enter cell senescence, the telomerase activity, chromosomal abnormality, and the ability to form tumors in vivo. Our studies showed that HUMSCs from all 10 donors ultimately entered senescence and did not undergo spontaneous malignant transformation. However, HUMSCs from two of the 10 donors treated with 3-MCA displayed an increased proliferation rate, failed to enter senescence, and exhibited an altered cell morphology. When these cells (tHUMSCs) were injected into immunodeficient mice, they gave rise to sarcoma-like or poorly differentiated tumors. Moreover, in contrast to HUMSCs, tHUMSCs showed a positive expression of human telomerase reverse transcriptase (hTERT) and did not exhibit a shortening of the relative telomere length during the long-term culture in vitro. Our studies demonstrate that HUMSCs are not susceptible to spontaneous malignant transformation. However, the malignant transformation could be induced by chemical carcinogen 3-MCA. PMID:24339974

Toward radioguided surgery with β- decays: uptake of a somatostatin analogue, DOTATOC, in meningioma and high-grade glioma.

PubMed

Collamati, Francesco; Pepe, Alessandra; Bellini, Fabio; Bocci, Valerio; Chiodi, Giacomo; Cremonesi, Marta; De Lucia, Erika; Ferrari, Mahila E; Frallicciardi, Paola M; Grana, Chiara M; Marafini, Michela; Mattei, Ilaria; Morganti, Silvio; Patera, Vincenzo; Piersanti, Luca; Recchia, Luigi; Russomando, Andrea; Sarti, Alessio; Sciubba, Adalberto; Senzacqua, Martina; Solfaroli Camillocci, Elena; Voena, Cecilia; Pinci, Davide; Faccini, Riccardo

2015-01-01

A novel radioguided surgery (RGS) technique for cerebral tumors using β(-) radiation is being developed. Checking for a radiotracer that can deliver a β(-) emitter to the tumor is a fundamental step in the deployment of such a technique. This paper reports a study of the uptake of (90)Y-DOTATOC in meningiomas and high-grade gliomas (HGGs) and a feasibility study of the RGS technique in these types of tumor. Estimates were performed assuming the use of a β(-) probe under development with a sensitive area 2.55 mm in radius to detect 0.1-mL residuals. Uptake and background from healthy tissues were estimated on (68)Ga-DOTATOC PET scans of 11 meningioma patients and 12 HGG patients. A dedicated statistical analysis of the DICOM images was developed and validated. The feasibility study was performed using full simulation of emission and detection of the radiation, accounting for the measured uptake and background rate. All meningioma patients but one with an atypical extracranial tumor showed high uptake of DOTATOC. In terms of feasibility of the RGS technique, we estimated that by administering a 3 MBq/kg activity of radiotracer, the time needed to detect a 0.1-mL remnant with 5% false-negative and 1% false-positive rates is less than 1 s. Actually, to achieve a detection time of 1 s the required activities to administer were as low as 0.2-0.5 MBq/kg in many patients. In HGGs, the uptake was lower than in meningiomas, but the tumor-to-nontumor ratio was higher than 4, which implies that the tracer can still be effective for RGS. It was estimated that by administering 3 mBq/kg of radiotracer, the time needed to detect a 0.1-mL remnant is less than 6 s, with the exception of the only oligodendroma in the sample. Uptake of (90)Y-DOTATOC in meningiomas was high in all studied patients. Uptake in HGGs was significantly worse than in meningiomas but was still acceptable for RGS, particularly if further research and development are done to improve the performance of the �

Association of human papilloma virus with atypical and malignant oral papillary lesions.

PubMed

McCord, Christina; Xu, Jing; Xu, Wei; Qiu, Xin; Muhanna, Nidal; Irish, Jonathan; Leong, Iona; McComb, Richard John; Perez-Ordonez, Bayardo; Bradley, Grace

2014-06-01

This study aimed to examine atypical and malignant papillary oral lesions for low- and high-risk human papillomavirus (HPV) infection and to correlate HPV infection with clinical and pathologic features. Sections of 28 atypical papillary lesions (APLs) and 14 malignant papillary lesions (MPLs) were examined for HPV by in situ hybridization and for p16 and MIB-1 by immunohistochemistry; 24 conventional papillomas were studied for comparison. Low-risk HPV was found in 10 of 66 cases, including 9 APLs and 1 papilloma. All low-risk HPV-positive cases showed suprabasilar MIB-1 staining, and the agreement was statistically significant (P < .0001). Diffuse p16 staining combined with high-risk HPV was not seen in any of the cases. A subset of HPV(-) APLs progressed to carcinoma. Oral papillary lesions are a heterogeneous group. Low-risk HPV infection is associated with a subset of APLs with a benign clinical course. Potentially malignant APLs and MPLs are not associated with low- or high-risk HPV. Copyright © 2014 Elsevier Inc. All rights reserved.

Harvey Cushing's Meningiomas text and the historical origin of resectability criteria for the anterior one third of the superior sagittal sinus.

PubMed

Shrivastava, Raj K; Segal, Salomao; Camins, Martin B; Sen, Chandranath; Post, Kalmon D

2003-10-01

The search for the origin of the commonly held principle in current neurosurgery regarding the resectability of the anterior one third of the superior sagittal sinus unravels the many fascinating developments that occurred in neurosurgery during the early 20th century. All these occurrences can be traced back to, and are uniquely contextualized in, Harvey Cushing's seminal text, Meningiomas, Their Classification, Regional Behaviour, Life History, and Surgical End Results. Written with Louise Eisenhardt and published in 1938, Meningiomas is a monograph of incredible description and detail. The meticulous categorization of meningiomas, their presentation, clinical outcome, and surgical therapies are even further supplemented by Cushing's personal commentary, questions, and recollections. Cushing's genius was evident in his ability not only to make insightful clinical observations, but also to synthesize these ideas within the neurosurgical context of his era. As he says in Meningiomas, "Thus the pathological curiosity of one day becomes in its proper time a commonplace... most of which are one and the same disorder--had, for their interpretation, to await the advent of the Neurosurgeon."

[Skull base meningiomas: a predictive system to know the extent of their surgical resection and patient outcome].

PubMed

Morales, F; Maillo, A; Díaz-Alvarez, A; Merino, M; Muñoz-Herrera, A; Hernández, J; Santamarta, D

2005-12-01

The aim of this study was to build a preoperative predictive system which could provide reliable information about: 1 degrees which skull base meningiomas can be total or partially removed, and 2 degrees their surgical outcome. Patient histories and imaging data were reviewed retrospectively from 85 consecutive skull base meningiomas patients who underwent surgery from 1990 and 2002. From the preoperative data, nine variables were selected for conventional statistical analysis as regards their relationship with: 1 degrees total vs partial tumor resection and 2 degrees with patients outcome according to the degree of tumour removal. From the nine variables analysed only two had a statistical association with the type of tumour resection performed (total vs partial) and the patient outcome: 1) arteries encasement and 2) cranial nerves involvement. Upon correlating these two variables with the type of tumour resection performed (total vs partial) and with the Karnofsky'scale to evaluate patients surgical outcome, the following grading groups were identified: Grade I: skull base meningiomas which did not involve cranial nerves or artery or only encased one artery or one cranial nerve. In these cases the incidence of gross tumour resection was 98.3% (p< 0.0001) and the perspective to reach 70 points in the Karnofsky'scale was of 96.5% ( p=0.001). Grade II: skull base meningiomas which involved one cranial nerve and encased, at least, two main cerebral arteries. In these cases, the frequency of total resection, decreased to 83.3% (p<0.0001) and the probability to reach 70 points in the Karnofsky'scale was 70.6% (p=0.001). Grade III: skull base meningiomas which involved two or more cranial nerves and encased several arteries In this group, the frequency of a total resection was of 42.9% (p<0.0001) and the probability of reaching 70 points in the Karnofsky'scale was only 60% (p=0.001). We propose a preoperative grading system for skull base meningiomas that helps

Wavelet-domain de-noising of OCT images of human brain malignant glioma

NASA Astrophysics Data System (ADS)

Dolganova, I. N.; Aleksandrova, P. V.; Beshplav, S.-I. T.; Chernomyrdin, N. V.; Dubyanskaya, E. N.; Goryaynov, S. A.; Kurlov, V. N.; Reshetov, I. V.; Potapov, A. A.; Tuchin, V. V.; Zaytsev, K. I.

2018-04-01

We have proposed a wavelet-domain de-noising technique for imaging of human brain malignant glioma by optical coherence tomography (OCT). It implies OCT image decomposition using the direct fast wavelet transform, thresholding of the obtained wavelet spectrum and further inverse fast wavelet transform for image reconstruction. By selecting both wavelet basis and thresholding procedure, we have found an optimal wavelet filter, which application improves differentiation of the considered brain tissue classes - i.e. malignant glioma and normal/intact tissue. Namely, it allows reducing the scattering noise in the OCT images and retaining signal decrement for each tissue class. Therefore, the observed results reveals the wavelet-domain de-noising as a prospective tool for improved characterization of biological tissue using the OCT.

Evaluation of the applicability of territorial arterial spin labeling in meningiomas for presurgical assessments compared with 3-dimensional time-of-flight magnetic resonance angiography.

PubMed

Lu, Yiping; Luan, Shihai; Liu, Li; Xiong, Ji; Wen, Jianbo; Qu, Jianxun; Geng, Daoying; Yin, Bo

2017-10-01

To prospectively evaluate the application of territorial arterial spin labelling (t-ASL) in comparison with unenhanced three-dimensional time-of-flight magnetic resonance angiography (3D-TOF-MRA) in the identification of the feeding vasculature of meningiomas. Thirty consecutive patients with suspected meningiomas underwent conventional MR imaging, unenhanced 3D-TOF-MRA and t-ASL scanning. Four experienced neuro-radiologists assessed the feeding vessels with different techniques separately. For the identification of the origin of the feeding arteries on t-ASL, the inter-observer agreement was excellent (к = 0.913), while the inter-observer agreement of 3D-TOF-MRA was good (к = 0.653). The inter-modality agreement between t-ASL and 3D-TOF-MRA for the feeding arteries was moderate (к = 0.514). All 8 patients with motor or sensory disorders proved to have meningiomas supplied completely or partially by the internal carotid arteries, while all 14 patients with meningiomas supplied by the external carotid arteries or basilar arteries didn't show any symptoms concerning motor or sensory disorders (p = 0.003). T-ASL could complement unenhanced 3D-TOF-MRA and increase accuracy in the identification of the supplying arteries of meningiomas in a safe, intuitive, non-radioactive manner. The information about feeding arteries was potentially related to patients' symptoms and pathology, making it more crucial for neurosurgeons in planning surgery as well as evaluating prognosis. • A comprehensive understanding of feeding vasculature is helpful for optimized treatment decisions. • T-ASL could identify main supplying arteries of meningiomas with excellent inter-observer agreement. • The inter-modality agreement for identification of the main feeding arteries was moderate. • Blood supply from ICAs was related to motor or sensory disorders. • High-level meningiomas were found to have double main supplying arteries.

[Support vector machine?assisted diagnosis of human malignant gastric tissues based on dielectric properties].

PubMed

Zhang, Sa; Li, Zhou; Xin, Xue-Gang

2017-12-20

To achieve differential diagnosis of normal and malignant gastric tissues based on discrepancies in their dielectric properties using support vector machine. The dielectric properties of normal and malignant gastric tissues at the frequency ranging from 42.58 to 500 MHz were measured by coaxial probe method, and the Cole?Cole model was used to fit the measured data. Receiver?operating characteristic (ROC) curve analysis was used to evaluate the discrimination capability with respect to permittivity, conductivity, and Cole?Cole fitting parameters. Support vector machine was used for discriminating normal and malignant gastric tissues, and the discrimination accuracy was calculated using k?fold cross? The area under the ROC curve was above 0.8 for permittivity at the 5 frequencies at the lower end of the measured frequency range. The combination of the support vector machine with the permittivity at all these 5 frequencies combined achieved the highest discrimination accuracy of 84.38% with a MATLAB runtime of 3.40 s. The support vector machine?assisted diagnosis is feasible for human malignant gastric tissues based on the dielectric properties.

Exposure to ionizing radiation during dental X-rays is not associated with risk of developing meningioma: a meta-analysis based on seven case-control studies.

PubMed

Xu, Ping; Luo, Hong; Huang, Guang-Lei; Yin, Xin-Hai; Luo, Si-Yang; Song, Ju-Kun

2015-01-01

Many observational studies have found that exposure to dental X-rays is associated with the risk of development of meningioma. However, these findings are inconsistent. We conducted a meta-analysis to assess the relationship between exposure to dental X-rays and the risk of development of meningioma. The PubMed and EMBASE databases were searched to identify eligible studies. Summary odds ratio (OR) estimates and 95% confidence intervals (95% CIs) were used to compute the risk of meningioma development according to heterogeneity. Subgroup and sensitivity analyses were performed to further explore the potential heterogeneity. Finally, publication bias was assessed. Seven case-control studies involving 6,174 patients and 19,459 controls were included in the meta-analysis. Neither exposure to dental X-rays nor performance of full-mouth panorex X-rays was associated with an increased risk of development of meningioma (overall: OR, 0.97; 95% CI, 0.70-1.32; dental X-rays: OR, 1.05; 95% CI, 0.89-1.25; panorex X-rays: OR, 1.01; 95% CI, 0.76-1.34). However, exposure to bitewing X-rays was associated with a slightly increased risk of development of meningioma (OR, 1.73; 95% CI, 1.28-2.34). Similar results were obtained in the subgroup and sensitivity analyses. Little evidence of publication bias was observed. Based on the currently limited data, there is no association between exposure to dental X-rays and the risk of development of meningioma. However, these results should be cautiously interpreted because of the heterogeneity among studies. Additional large, high-quality clinical trials are needed to evaluate the association between exposure to dental X-rays and the risk of development of meningioma.

c-RET Molecule in Malignant Melanoma from Oncogenic RET-Carrying Transgenic Mice and Human Cell Lines

PubMed Central

Takeda, Kozue; Iida, Machiko; Kumasaka, Mayuko; Matsumoto, Yoshinari; Kato, Masashi

2010-01-01

Malignant melanoma is one of the most aggressive cancers and its incidence worldwide has been increasing at a greater rate than that of any other cancer. We previously reported that constitutively activated RFP-RET-carrying transgenic mice (RET-mice) spontaneously develop malignant melanoma. In this study, we showed that expression levels of intrinsic c-Ret, glial cell line-derived neurotrophic factor (Gdnf) and Gdnf receptor alpha 1 (Gfra1) transcripts in malignant melanomas from RET-transgenic mice were significantly upregulated compared with those in benign melanocytic tumors. These results suggest that not only introduced oncogenic RET but also intrinsic c-Ret/Gdnf are involved in murine melanomagenesis in RET-mice. We then showed that c-RET and GDNF transcript expression levels in human malignant melanoma cell lines (HM3KO and MNT-1) were higher than those in primary cultured normal human epithelial melanocytes (NHEM), while GFRa1 transcript expression levels were comparable among NHEM, HM3KO and MNT-1. We next showed c-RET and GFRa1 protein expression in HM3KO cells and GDNF-mediated increased levels of their phosphorylated c-RET tyrosine kinase and signal transduction molecules (ERK and AKT) sited potentially downstream of c-RET. Taken together with the finding of augmented proliferation of HM3KO cells after GDNF stimulation, our results suggest that GDNF-mediated c-RET kinase activation is associated with the pathogenesis of malignant melanoma. PMID:20422010

c-RET molecule in malignant melanoma from oncogenic RET-carrying transgenic mice and human cell lines.

PubMed

Ohshima, Yuichiro; Yajima, Ichiro; Takeda, Kozue; Iida, Machiko; Kumasaka, Mayuko; Matsumoto, Yoshinari; Kato, Masashi

2010-04-21

Malignant melanoma is one of the most aggressive cancers and its incidence worldwide has been increasing at a greater rate than that of any other cancer. We previously reported that constitutively activated RFP-RET-carrying transgenic mice (RET-mice) spontaneously develop malignant melanoma. In this study, we showed that expression levels of intrinsic c-Ret, glial cell line-derived neurotrophic factor (Gdnf) and Gdnf receptor alpha 1 (Gfra1) transcripts in malignant melanomas from RET-transgenic mice were significantly upregulated compared with those in benign melanocytic tumors. These results suggest that not only introduced oncogenic RET but also intrinsic c-Ret/Gdnf are involved in murine melanomagenesis in RET-mice. We then showed that c-RET and GDNF transcript expression levels in human malignant melanoma cell lines (HM3KO and MNT-1) were higher than those in primary cultured normal human epithelial melanocytes (NHEM), while GFRa1 transcript expression levels were comparable among NHEM, HM3KO and MNT-1. We next showed c-RET and GFRa1 protein expression in HM3KO cells and GDNF-mediated increased levels of their phosphorylated c-RET tyrosine kinase and signal transduction molecules (ERK and AKT) sited potentially downstream of c-RET. Taken together with the finding of augmented proliferation of HM3KO cells after GDNF stimulation, our results suggest that GDNF-mediated c-RET kinase activation is associated with the pathogenesis of malignant melanoma.

Results of stereotactic radiosurgery for patients with imaging defined cavernous sinus meningiomas

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pollock, Bruce E.; Stafford, Scott L.

2005-08-01

Introduction: The purpose of this study was to evaluate the efficacy and safety of stereotactic radiosurgery as primary management for patients with imaging defined cavernous sinus meningiomas. Methods: Between 1992 and 2001, 49 patients had radiosurgery for dural-based masses of the cavernous sinus presumed to be meningiomas. The mean patient age was 55.5 years. The mean tumor volume was 10.2 mL; the mean tumor margin dose was 15.9 Gy. The mean follow-up was 58 months (range, 16-144 months). Results: No tumor enlarged after radiosurgery. Twelve of 38 patients (26%) with preexisting diplopia or facial numbness/pain had improvement in cranial nervemore » function. Five patients (10%) had new (n = 3) or worsened (n = 2) trigeminal dysfunction; 2 of these patients (4%) underwent surgery at 20 and 25 months after radiosurgery despite no evidence of tumor progression. Neither patient improved after partial tumor resection. One patient (2%) developed an oculomotor nerve injury. One patient (2%) had an ischemic stroke related to occlusion of the cavernous segment of the internal carotid artery. Event-free survival was 98%, 85%, and 80% at 1, 3, and 7 years after radiosurgery, respectively. Univariate analysis of patient and dosimetric factors found no analyzed factor correlated with postradiosurgical morbidity. Conclusions: Radiosurgery was an effective primary management strategy for patients with an imaging defined cavernous sinus meningioma. Except in situations of symptomatic mass effect, unusual clinical presentation, or atypical imaging features, surgery to confirm the histologic diagnosis is unlikely to provide clinical benefit.« less

Meningioma patients diagnosed 2007–2009 and the association with use of mobile and cordless phones: a case–control study

PubMed Central

2013-01-01

Background To study the association between use of wireless phones and meningioma. Methods We performed a case–control study on brain tumour cases of both genders aged 18–75 years and diagnosed during 2007–2009. One population-based control matched on gender and age was used to each case. Here we report on meningioma cases including all available controls. Exposures were assessed by a questionnaire. Unconditional logistic regression analysis was performed. Results In total 709 meningioma cases and 1,368 control subjects answered the questionnaire. Mobile phone use in total produced odds ratio (OR) = 1.0, 95% confidence interval (CI) = 0.7-1.4 and cordless phone use gave OR = 1.1, 95% CI = 0.8-1.5. The risk increased statistically significant per 100 h of cumulative use and highest OR was found in the fourth quartile (>2,376 hours) of cumulative use for all studied phone types. There was no statistically significant increased risk for ipsilateral mobile or cordless phone use, for meningioma in the temporal lobe or per year of latency. Tumour volume was not related to latency or cumulative use in hours of wireless phones. Conclusions No conclusive evidence of an association between use of mobile and cordless phones and meningioma was found. An indication of increased risk was seen in the group with highest cumulative use but was not supported by statistically significant increasing risk with latency. Results for even longer latency periods of wireless phone use than in this study are desirable. PMID:23870102

Simpson grading as predictor of meningioma recurrence.

PubMed

Quddusi, Ayesha; Shamim, Muhammad Shahzad

2018-05-01

Meningimas are one of the commonest primary brain tumours and the commonest extra-axial primary brain tumour. Despite better understanding of the molecular pathogenesis of the tumours, surgical excision remains the treatment of choice, and in a large proportion of cases, complete excision is curative. Simpson grading for the extent of resection of meningiomas, was introduced more than six decades ago, and has stood the test of time. With modern technological advancements, however, the relevance of Simpson grading has been questioned. Herein we review the recent literature on the relevance of Simpson grading more than sixty years after its introduction.

Modern Microsurgical Resection of Olfactory Groove Meningiomas by Classical Bicoronal Subfrontal Approach without Orbital Osteotomies

PubMed Central

Farooq, Ghulam; Rehman, Lal; Bokhari, Irum; Rizvi, Syed Raza Hussain

2018-01-01

Background: The olfactory groove meningioma has always been surgically challenging. The common microscopic surgical procedures exercised involve modification of pterional or sub-frontal approaches with or without orbital osteotomies. However, we believe that orbital osteotomies are not mandatory to achieve gross total resection. Hence, this study was performed to evaluate the surgical outcomes of olfactory groove meningioma with bicoronal sub frontal approach but without orbital osteotomies. Materials and Methods: The study was performed by reviewing the medical charts, neuroimaging data, and follow-up data of 19 patients who were treated micro surgically for olfactory groove meningioma without orbital osteotomies in our department. Mean overall follow up period of our study was 5 years. Statistical analysis was done by means of IBM SPSS Software version 19. Results: Nineteen patients (1 male and 18 female patients, with an age range of 35-67 years; average age of patients' 51±7.5 years) of OGM were managed in our department. All patients were evaluated by MRI Brain with and without Gadolinium, CTA, CT Scan both axial and Coronal sequences. Most common symptom reported was head ache (80%), others include; urinary incontinence (26%), seizures (78%), decreased visual acuity (79%), papilledema (74%), personality changes (68%) and olfactory loss was reported in 57% of the patients. Post-operative complications include; CSF accumulation (5%), hematoma at tumor bed (10%), skin infection (5%) and mild post-operative brain edema (26%). Mortality rate was 5%. During 5 years of follow-up, we recorded one recurrence which was after 26 months and successfully removed in reoperation. Conclusion: Bi-coronal sub frontal approach appears to be an excellent technique for Olfactory Meningioma removal as practiced by most neurosurgeons. Nevertheless, it is not mandatory to carry out orbital osteotomy to acquire optimal surgical outcome as is advocated by some Authors. PMID:29682018

Modern Microsurgical Resection of Olfactory Groove Meningiomas by Classical Bicoronal Subfrontal Approach without Orbital Osteotomies.

PubMed

Farooq, Ghulam; Rehman, Lal; Bokhari, Irum; Rizvi, Syed Raza Hussain

2018-01-01

The olfactory groove meningioma has always been surgically challenging. The common microscopic surgical procedures exercised involve modification of pterional or sub-frontal approaches with or without orbital osteotomies. However, we believe that orbital osteotomies are not mandatory to achieve gross total resection. Hence, this study was performed to evaluate the surgical outcomes of olfactory groove meningioma with bicoronal sub frontal approach but without orbital osteotomies. The study was performed by reviewing the medical charts, neuroimaging data, and follow-up data of 19 patients who were treated micro surgically for olfactory groove meningioma without orbital osteotomies in our department. Mean overall follow up period of our study was 5 years. Statistical analysis was done by means of IBM SPSS Software version 19. Nineteen patients (1 male and 18 female patients, with an age range of 35-67 years; average age of patients' 51±7.5 years) of OGM were managed in our department. All patients were evaluated by MRI Brain with and without Gadolinium, CTA, CT Scan both axial and Coronal sequences. Most common symptom reported was head ache (80%), others include; urinary incontinence (26%), seizures (78%), decreased visual acuity (79%), papilledema (74%), personality changes (68%) and olfactory loss was reported in 57% of the patients. Post-operative complications include; CSF accumulation (5%), hematoma at tumor bed (10%), skin infection (5%) and mild post-operative brain edema (26%). Mortality rate was 5%. During 5 years of follow-up, we recorded one recurrence which was after 26 months and successfully removed in reoperation. Bi-coronal sub frontal approach appears to be an excellent technique for Olfactory Meningioma removal as practiced by most neurosurgeons. Nevertheless, it is not mandatory to carry out orbital osteotomy to acquire optimal surgical outcome as is advocated by some Authors.

Stereotactic Radiosurgery in Treating Patients With Brain Tumors

ClinicalTrials.gov

2012-03-21

Adult Central Nervous System Germ Cell Tumor; Adult Malignant Meningioma; Adult Medulloblastoma; Adult Noninfiltrating Astrocytoma; Adult Oligodendroglioma; Adult Craniopharyngioma; Adult Meningioma; Brain Metastases; Adult Ependymoma; Adult Pineal Parenchymal Tumor; Adult Brain Stem Glioma; Adult Infiltrating Astrocytoma; Mixed Gliomas; Stage IV Peripheral Primitive Neuroectodermal Tumor

Arsenic-induced malignant transformation of human keratinocytes: Involvement of Nrf2

PubMed Central

Pi, Jingbo; Diwan, Bhalchandra A.; Sun, Yang; Liu, Jie; Qu, Wei; He, Yuying; Styblo, Miroslav; Waalkes, Michael P.

2009-01-01

Arsenic is a well-known human skin carcinogen but the underlying mechanisms of carcinogenesis are unclear. Transcription factor Nrf2-mediated antioxidant response represents a critical cellular defense mechanism, and emerging data suggest that constitutive activation of Nrf2 contributes to malignant phenotype. In the present study when an immortalized, non-tumorigenic human keratinocyte cell line (HaCaT) was continuously exposed to environmentally relevant level of inorganic arsenite (100 nM) for 28 weeks, malignant transformation occurred as evidenced by the formation of highly aggressive squamous cell carcinoma after inoculation into nude mice. To investigate the mechanisms involved, a broad array of biomarkers for transformation were assessed in these arsenic-transformed cells (termed As-TM). In addition to increased secretion of matrix metalloproteinase-9 (MMP-9), a set of markers for squamous differentiation and skin keratinization, including keratin-1, keratin-10, involucrin, and loricrin, were significantly elevated in As-TM cells. Furthermore, As-TM cells showed increased intracellular glutathione, elevated expression of Nrf2 and its target genes, as well as generalized apoptotic resistance. In contrast to increased basal Nrf2 activity in As-TM cells, a diminished Nrf2-mediated antioxidant response induced by acute exposure to high dose of arsenite or tert-butyl hydroxyquinone occurred. The findings that multiple biomarkers for malignant transformation observed in As-TM cells, including MMP-9 and cytokeratins, are potentially regulated by Nrf2 suggest constitutive Nrf2 activation may be involved in arsenic carcinogenesis of skin. The weakened Nrf2 activation in response to oxidative stressors observed in As-TM cells, coupled with acquired apoptotic resistance, would potentially have increased the likelihood of transmittable oxidative DNA damage and fixation of mutational/DNA damage events. PMID:18572023

Adenovirus-mediated suppression of HMGI(Y) protein synthesis as potential therapy of human malignant neoplasias

PubMed Central

Scala, Stefania; Portella, Giuseppe; Fedele, Monica; Chiappetta, Gennaro; Fusco, Alfredo

2000-01-01

High mobility group I (HMGI) proteins are overexpressed in several human malignant tumors. We previously demonstrated that inhibition of HMGI synthesis prevents thyroid cell transformation. Here, we report that an adenovirus carrying the HMGI(Y) gene in an antisense orientation (Ad-Yas) induced programmed cell death of two human thyroid anaplastic carcinoma cell lines (ARO and FB-1), but not normal thyroid cells. The Ad-Yas virus led to death of lung, colon, and breast carcinoma cells. A control adenovirus carrying the lacZ gene did not inhibit the growth of either normal or neoplastic cells. Ad-Yas treatment of tumors induced in athymic mice by ARO cells caused a drastic reduction in tumor size. Therefore, suppression of HMGI(Y) protein synthesis by an HMGI(Y) antisense adenoviral vector may be a useful treatment strategy in a variety of human malignant neoplasias, in which HMGI(Y) gene overexpression is a general event. PMID:10759549

Using a Guided Machine Learning Ensemble Model to Predict Discharge Disposition following Meningioma Resection.

PubMed

Muhlestein, Whitney E; Akagi, Dallin S; Kallos, Justiss A; Morone, Peter J; Weaver, Kyle D; Thompson, Reid C; Chambless, Lola B

2018-04-01

Objective  Machine learning (ML) algorithms are powerful tools for predicting patient outcomes. This study pilots a novel approach to algorithm selection and model creation using prediction of discharge disposition following meningioma resection as a proof of concept. Materials and Methods  A diversity of ML algorithms were trained on a single-institution database of meningioma patients to predict discharge disposition. Algorithms were ranked by predictive power and top performers were combined to create an ensemble model. The final ensemble was internally validated on never-before-seen data to demonstrate generalizability. The predictive power of the ensemble was compared with a logistic regression. Further analyses were performed to identify how important variables impact the ensemble. Results  Our ensemble model predicted disposition significantly better than a logistic regression (area under the curve of 0.78 and 0.71, respectively, p  = 0.01). Tumor size, presentation at the emergency department, body mass index, convexity location, and preoperative motor deficit most strongly influence the model, though the independent impact of individual variables is nuanced. Conclusion  Using a novel ML technique, we built a guided ML ensemble model that predicts discharge destination following meningioma resection with greater predictive power than a logistic regression, and that provides greater clinical insight than a univariate analysis. These techniques can be extended to predict many other patient outcomes of interest.

Significance of tumor volume related to peritumoral edema in intracranial meningioma treated with extreme hypofractionated stereotactic radiation therapy in three to five fractions.

PubMed

Morimoto, Masahiro; Yoshioka, Yasuo; Shiomi, Hiroya; Isohashi, Fumiaki; Konishi, Koji; Kotsuma, Tadayuki; Fukuda, Shoichi; Kagawa, Naoki; Kinoshita, Manabu; Hashimoto, Naoya; Yoshimine, Toshiki; Koizumi, Masahiko

2011-05-01

To investigate the treatment results of intracranial meningiomas treated with hypofractionated stereotactic radiation therapy in three to five fractions. Thirty-one patients (32 lesions) with intracranial meningioma were treated with hypofractionated stereotactic radiation therapy in three to five fractions using CyberKnife. Fifteen lesions were diagnosed as Grade I (World Health Organization classification) by surgical resection and 17 lesions were diagnosed as meningioma based on radiological findings. The median follow-up time was 48 months. The median planning target volume was 6.3 cm(3) (range, 1.4-27.1), and the prescribed dose (D90≤) ranged from 21 to 36 Gy (median, 27.8) administrated in three to five fractions. Five-year overall and progression-free survival rate of all 31 patients with intracranial meningioma was 86 and 83%, respectively. Five-year progression-free rate of all 32 lesions was 87%. Six of the 31 patients (19%) developed marked peritumoral edema, three of whom were asymptomatic and three symptomatic, the latter with late adverse effects of more than or equal to Grade 3. The mean planning target volume of the six lesions with marked peritumoral edema was 15.6 cm(3), and for the remaining 26 lesions without marked peritumoral edema was 7.1 cm(3) (P = 0.004). The threshold diameter of 2.56 cm for meningioma was calculated from the planning target volume (11 cm(3)) and was used as marker of developing peritumoral edema (P = 0.003). Tumor volume is a significant indicative factor for peritumoral edema in intracranial meningioma treated with hypofractionated stereotactic radiation therapy in three to five factions.

Unilateral external and internal ophthalmoplegia caused by intracranial meningioma in a dog.

PubMed

Larocca, R.D.

2000-01-01

Unilateral internal and external ophthalmoplegia caused by an intracranial meningioma occurred in a 15-year-old Belgian Sheepdog. The dog initially presented with ventro-lateral strabismus of the left eye, and ptosis of the left upper eyelid. Anisocoria was present with the left pupil fixed and dilated. Both eyes were visual. Neuro-ophthalmic evaluation revealed a lesion located in the left oculomotor nerve. Pharmacological testing with dilute pilocarpine (0.1% in artificial tears) revealed evidence of parasympathetic denervation of the left eye. Further evaluation via magnetic resonance imaging (MRI) revealed a well-defined mass to the left of midline and lateral to the sella turcica. An attempt was made to excise/debulk the mass due to worsening conditions and the dog died the following day. Necropsy revealed a mass of randomly arranged bundles and streams of spindle cells. Immunohistochemistry demonstrated a strong avidity for vimentin and a negative response for S-100 protein. These findings suggest a diagnosis of meningioma.

Histogram Profiling of Postcontrast T1-Weighted MRI Gives Valuable Insights into Tumor Biology and Enables Prediction of Growth Kinetics and Prognosis in Meningiomas.

PubMed

Gihr, Georg Alexander; Horvath-Rizea, Diana; Kohlhof-Meinecke, Patricia; Ganslandt, Oliver; Henkes, Hans; Richter, Cindy; Hoffmann, Karl-Titus; Surov, Alexey; Schob, Stefan

2018-06-14

Meningiomas are the most frequently diagnosed intracranial masses, oftentimes requiring surgery. Especially procedure-related morbidity can be substantial, particularly in elderly patients. Hence, reliable imaging modalities enabling pretherapeutic prediction of tumor grade, growth kinetic, realistic prognosis, and-as a consequence-necessity of surgery are of great value. In this context, a promising diagnostic approach is advanced analysis of magnetic resonance imaging data. Therefore, our study investigated whether histogram profiling of routinely acquired postcontrast T1-weighted images is capable of separating low-grade from high-grade lesions and whether histogram parameters reflect Ki-67 expression in meningiomas. Pretreatment T1-weighted postcontrast volumes of 44 meningioma patients were used for signal intensity histogram profiling. WHO grade, tumor volume, and Ki-67 expression were evaluated. Comparative and correlative statistics investigating the association between histogram profile parameters and neuropathology were performed. None of the investigated histogram parameters revealed significant differences between low-grade and high-grade meningiomas. However, significant correlations were identified between Ki-67 and the histogram parameters skewness and entropy as well as between entropy and tumor volume. Contrary to previously reported findings, pretherapeutic postcontrast T1-weighted images can be used to predict growth kinetics in meningiomas if whole tumor histogram analysis is employed. However, no differences between distinct WHO grades were identifiable in out cohort. As a consequence, histogram analysis of postcontrast T1-weighted images is a promising approach to obtain quantitative in vivo biomarkers reflecting the proliferative potential in meningiomas. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Prognostic significance of MYCN gene amplification and protein expression in primary brain tumors: Astrocytoma and meningioma.

PubMed

Estiar, Mehrdad Asghari; Javan, Firouzeh; Zekri, Ali; Mehrazin, Masoud; Mehdipour, Parvin

2017-07-04

Astrocytoma and meningioma are the most common primary brain tumors. MYCN as a member of MYC proto-oncogenes has recently appeared as an attractive therapeutic target. Functions of MYCN are critical for growth of nervous system and neural differentiation. We examined MYCN amplification and protein expression in astrocytoma and meningioma cases. In this study, we used real-time PCR, FISH assay and flowcytometry to analyze DNA amplification and protein expression of MYCN. Among 30 samples of brain tumor, 14 cases (46.6%) revealed MYCN amplification. High-protein expression of MYCN was also observed in 43.3% of patients. There was a significant correlation between MYCN gene amplification and protein expression (r= 0.523; p= 0.003), interestingly five case showed discrepancy between the gene amplification and protein expression. Although MYCN amplification fails to show correlation with poor prognosis (p= 0.305), protein high-expression of MYCN significantly reduce disease-free survival (p= 0.019). Our results challenge the concept of the neural specificity of MYCN by demonstrating contribution of MYCN in meningioma. Moreover, this study highlights the importance of research at both level of DNA and protein, to determine the biological functions and medical impacts of MYCN.

Intracranial meningioma causing partial amaurosis in a cat.

PubMed

Goulle, Frédéric; Meige, Frédéric; Durieux, Franck; Malet, Christophe; Toulza, Olivier; Isard, Pierre-François; Peiffer, Robert L; Dulaurent, Thomas

2011-09-01

To describe a case of intracranial meningioma causing visual impairment in a cat, successfully treated by surgery. An adult neutered male domestic cat was referred with a 10-month history of progressive visual impairment and altered behavior. Investigations included physical, ophthalmologic and neurological examinations as well as hematology, serum biochemistry and CT scan of the head. The menace response was absent in the left eye and decreased in the right eye. Electroretinograms were normal on both eyes, as was ophthalmic examination, ruling out an ocular cause and allowing a presumptive diagnosis of partial amaurosis due to a post-retinal lesion. CT scan demonstrated a large sessile extra axial mass along the right parietal bone and thickening of the adjacent bone. Cerebrospinal fluid was not collected because high intracranial pressure represented a risk for brain herniation. A right rostrotentorial craniectomy was performed to remove the tumor. Ten days after surgery, vision was improved, neurological examination was normal and normal behavior was restored. Ten months after surgery, ophthalmological examination showed no visual deficit and CT scan did not reveal any sign of recurrence. Advanced imaging techniques allow veterinarians to detect early cerebral diseases and to provide specific treatment when it is possible. In cases of feline amaurosis due to intracranial meningioma, the vital prognosis is good while the visual prognosis is more uncertain, but recovery of normal vision and normal behavior is possible as demonstrated in the present case. © 2011 American College of Veterinary Ophthalmologists.

HMGB1 targeting by ethyl pyruvate suppresses malignant phenotype of human mesothelioma.

PubMed

Pellegrini, Laura; Xue, Jiaming; Larson, David; Pastorino, Sandra; Jube, Sandro; Forest, Kelly H; Saad-Jube, Zeyana Salim; Napolitano, Andrea; Pagano, Ian; Negi, Vishal S; Bianchi, Marco E; Morris, Paul; Pass, Harvey I; Gaudino, Giovanni; Carbone, Michele; Yang, Haining

2017-04-04

Human malignant mesothelioma (MM) is an aggressive cancer linked to asbestos and erionite exposure. We previously reported that High-Mobility Group Box-1 protein (HMGB1), a prototypic damage-associated molecular pattern, drives MM development and sustains MM progression. Moreover, we demonstrated that targeting HMGB1 inhibited MM cell growth and motility in vitro, reduced tumor growth in vivo, and prolonged survival of MM-bearing mice. Ethyl pyruvate (EP), the ethyl ester of pyruvic acid, has been shown to be an effective HMGB1 inhibitor in inflammation-related diseases and several cancers. Here, we studied the effect of EP on the malignant phenotype of MM cells in tissue culture and on tumor growth in vivo using an orthotopic MM xenograft model. We found that EP impairs HMGB1 secretion by MM cells leading to reduced RAGE expression and NF-κB activation. As a consequence, EP impaired cell motility, cell proliferation, and anchorage-independent growth of MM cells. Moreover, EP reduced HMGB1 serum levels in mice and inhibited the growth of MM xenografts.Our results indicate that EP effectively hampers the malignant phenotype of MM, offering a novel potential therapeutic approach to patients afflicted with this dismal disease.

[Clinical characteristics and results of surgical treatment of petroclival meningioma].

PubMed

Tasić, Goran; Jovanović, Vladimir; Radulović, Danilo; Djurović, Branko; Piscević, Ivan; Nikolić, Igor; Janićijević, Milos

2006-01-01

The size of meningioma and its relation with neurovascular structures in petroclival region stipulate the degree of surgical radicalism and determine an operation risk. In spite of progress of surgical technology, the rate of surgical morbidity in view of cranial nerves deficit is 30%-50%. The objective of our study was to present the results of treatment of patients with petroclival meningiomas and to point to correlation of preoperative radiological findings and intraoperative results as well as neurological status of patients before and after surgical treatment. Retrospective analysis of 35 operated petroclival meningiomas at the Institute of Neurosurgery, CCS, in the period from 1995 to 2004 was presented. The following parameters were analyzed: size of tumor, relation with bone and neurovascular structures, preoperative condition, degree of surgical radicalism and postoperative outcome. The size of tumor was classified in four groups. There were 20 tumors at the right, and 15 at the left side. At the time of diagnostic procedures (based on CT and MRI), 20 tumors were in contact with brainstem, 9 compressed the brainstem, and 6 obstructed the IV ventricle. Preoperative patient condition was evaluated by Karnofsky index. Mean value for group I was 90, II - 80, III - 70 and IV - 50. In 9 cases, liquor drainage was performed preoperatively. In 3 cases, external liquor drainage was carried out postoperatively, and in one case it was replaced by permanent liquor drainage. Radical operation was performed in 44%, and significant reduction was done in other cases. In the postoperative period, 11% patients died, 28% had cranial nerves deficit, and pyramid deficit was recorded in 14% of the patients. The tumor size (III-IV) and brainstem compression were found to be statistically significant (p<0.05) as predisposed factors of deficit prolongation. Petroclival meningoma surgery is required upon precise preoperative analysis. Radicalism of operation is reserved for small

Classification of normal and malignant human gastric mucosa tissue with confocal Raman microspectroscopy and wavelet analysis

NASA Astrophysics Data System (ADS)

Hu, Yaogai; Shen, Aiguo; Jiang, Tao; Ai, Yong; Hu, Jiming

2008-02-01

Thirty-two samples from the human gastric mucosa tissue, including 13 normal and 19 malignant tissue samples were measured by confocal Raman microspectroscopy. The low signal-to-background ratio spectra from human gastric mucosa tissues were obtained by this technique without any sample preparation. Raman spectral interferences include a broad featureless sloping background due to fluorescence and noise. They mask most Raman spectral feature and lead to problems with precision and quantitation of the original spectral information. A preprocessed algorithm based on wavelet analysis was used to reduce noise and eliminate background/baseline of Raman spectra. Comparing preprocessed spectra of malignant gastric mucosa tissues with those of counterpart normal ones, there were obvious spectral changes, including intensity increase at ˜1156 cm -1 and intensity decrease at ˜1587 cm -1. The quantitative criterion based upon the intensity ratio of the ˜1156 and ˜1587 cm -1 was extracted for classification of the normal and malignant gastric mucosa tissue samples. This could result in a new diagnostic method, which would assist the early diagnosis of gastric cancer.

From The Cover: Reconstruction of functionally normal and malignant human breast tissues in mice

NASA Astrophysics Data System (ADS)

Kuperwasser, Charlotte; Chavarria, Tony; Wu, Min; Magrane, Greg; Gray, Joe W.; Carey, Loucinda; Richardson, Andrea; Weinberg, Robert A.

2004-04-01

The study of normal breast epithelial morphogenesis and carcinogenesis in vivo has largely used rodent models. Efforts at studying mammary morphogenesis and cancer with xenotransplanted human epithelial cells have failed to recapitulate the full extent of development seen in the human breast. We have developed an orthotopic xenograft model in which both the stromal and epithelial components of the reconstructed mammary gland are of human origin. Genetic modification of human stromal cells before the implantation of ostensibly normal human mammary epithelial cells resulted in the outgrowth of benign and malignant lesions. This experimental model allows for studies of human epithelial morphogenesis and differentiation in vivo and underscores the critical role of heterotypic interactions in human breast development and carcinogenesis.

Stereotactic Radiosurgery for Benign (World Health Organization Grade I) Cavernous Sinus Meningiomas-International Stereotactic Radiosurgery Society (ISRS) Practice Guideline: A Systematic Review.

PubMed

Lee, Cheng-Chia; Trifiletti, Daniel M; Sahgal, Arjun; DeSalles, Antonio; Fariselli, Laura; Hayashi, Motohiro; Levivier, Marc; Ma, Lijun; Álvarez, Roberto Martínez; Paddick, Ian; Regis, Jean; Ryu, Samuel; Slotman, Ben; Sheehan, Jason

2018-03-15

Stereotactic radiosurgery (SRS) has become popular as a standard treatment for cavernous sinus (CS) meningiomas. To summarize the published literature specific to the treatment of CS meningioma with SRS found through a systematic review, and to create recommendations on behalf of the International Stereotactic Radiosurgery Society. Articles published from January 1963 to December 2014 were systemically reviewed. Three electronic databases, PubMed, EMBASE, and The Cochrane Central Register of Controlled Trials, were searched. Publications in English with at least 10 patients (each arm) were included. Of 569 screened abstracts, a total of 49 full-text articles were included in the analysis. All studies were retrospective. Most of the reports had favorable outcomes with 5-yr progression-free survival (PFS) rates ranging from 86% to 99%, and 10-yr PFS rates ranging from 69% to 97%. The post-SRS neurological preservation rate ranged from 80% to 100%. Resection can be considered for the treatment of larger (>3 cm in diameter) and symptomatic CS meningioma in patients both receptive to and medically eligible for open surgery. Adjuvant or salvage SRS for residual or recurrent tumor can be utilized depending on factors such as tumor volume and proximity to adjacent critical organs at risk. The literature is limited to level III evidence with respect to outcomes of SRS in patients with CS meningioma. Based on the observed results, SRS offers a favorable benefit to risk profile for patients with CS meningioma.

Microsurgical treatment for central gyrus region meningioma with epilepsy as primary symptom.

PubMed

Deng, Wen-shuai; Zhou, Xiao-yang; Li, Zhao-jian; Xie, Hong-wei; Fan, Ming-chao; Sun, Peng

2014-09-01

The objective of this article was to investigate the operation outcome, complications, and the patient's quality of life after surgical therapy for central gyrus region meningioma with epilepsy as the primary symptom. All patients get at least 6 months of follow-up (range, 6-34 mo) after surgery. They underwent preoperative magnetic resonance imaging and video electroencephalography, and their clinical manifestations, imaging characteristics, microsurgical methods, and prognosis were retrospectively analyzed. The meningioma was located in the front and back of the central sulcus vein in 3 and 2 patients, respectively; in the compressed precentral gyrus and central sulcus vein in 3 patients; and in the precentral gyrus and postcentral gyrus each in 1 patient; beside the right sagittal sinus and invaded a thick draining vein on the brain surface in 1 patient and beside the right sagittal sinus and close to the precentral gyrus in 2 patients; invaded the superior sagittal sinus in 8 patients; crossed the cerebral falx and compressed cortex gyrus veins in 1 patient; invaded duramater and irritated skull hyperplasia in 3 patients; invaded duramater and its midline infiltrated into the superior sagittal sinus, was located behind the precentral gyrus, and enveloped the central sulcus vein. They were resected and classified by Simpson standards: 17 of the 26 patients had grade I, 6 patients had in grade II, and 3 patients had in grade III. Resection of central gyrus region meningioma by microsurgical technique avoids injury to the cerebral cortex, central sulcus vein, and other draining veins. Microsurgery improves the total resection rate, reduces recurrence rate, and lowers disability or death rate.

Characterization of brain tumours with spin-spin relaxation: pilot case study reveals unique T 2 distribution profiles of glioblastoma, oligodendroglioma and meningioma.

PubMed

Laule, Cornelia; Bjarnason, Thorarin A; Vavasour, Irene M; Traboulsee, Anthony L; Wayne Moore, G R; Li, David K B; MacKay, Alex L

2017-11-01

Prolonged spin-spin relaxation times in tumour tissue have been observed since some of the earliest nuclear magnetic resonance investigations of the brain. Over the last three decades, numerous studies have sought to characterize tumour morphology and malignancy using quantitative assessment of T 2 relaxation times, although attempts to categorize and differentiate tumours have had limited success. However, previous work must be interpreted with caution as relaxation data were typically acquired using a variety of multiple echo sequences with a range of echoes and T 2 decay curves and were frequently fit with monoexponential analysis. We defined the distribution of T 2 components in three different human brain tumours (glioblastoma, oligodendroglioma, meningioma) using a multi-echo sequence with a greater number of echoes and a longer acquisition window than previously used (48 echoes, data collection out to 1120 ms) with no a priori assumptions about the number of exponential components contributing to the T 2 decay. T 2 relaxation times were increased in tumour tissue and each tumour showed a distinct T 2 distribution profile. Tumours have complex and unique compartmentalization characteristics. Quantitative assessment of T 2 relaxation in brain cancer may be useful in evaluating different grades of brain tumours on the basis of their T 2 distribution profile, and has the potential to be a non-invasive diagnostic tool which may also be useful in monitoring therapy. Further study with a larger sample size and varying grades of tumours is warranted.

Angiomatous lesion and delayed cyst formation after gamma knife surgery for intracranial meningioma: case report and review of literatures.

PubMed

Liu, Zhiyong; He, Min; Chen, Hongxu; Liu, Yi; Li, Qiang; Li, Lin; Li, Jin; Chen, Haifeng; Xu, Jianguo

2015-01-01

Gamma Knife has become a major therapeutic method for intracranial meningiomas, vascular malformations and schwannomas with exact effect. In recent years an increasing number of delayed complications after Gamma Knife surgery have been reported, such as secondary tumors, cystic changes or cyst formation. But angiomatous lesion and delayed cyst formation after Gamma Knife for intracranial lesion has rarely been reported. Here we report the first case of angiomatous lesion and delayed cyst formation following Gamma Knife for intracranial meningioma and discuss its pathogenesis.

Cytologic appearance of retinal cells included in a fine-needle aspirate of a meningioma around the optic nerve of a dog.

PubMed

Tvedten, Harold; Hillström, Anna

2013-06-01

A 6-year-old Wirehair Dachshund had a meningioma around the optic nerve that caused exophthalmos. A benign mesenchymal tumor was suspected based on the cytologic pattern of a fine-needle aspirate, and a meningioma was diagnosed by histopathologic examination. In addition to the meningioma cells, the cytologic smears included groups of cells from apparently 4 layers of normal retina. In particular, uniform rod-shaped structures in the cytologic sample could suggest rod-shaped bacteria, but these structures were identified as cylindrical outer segments of photoreceptor rod cells. Other retinal structures recognized included pigmented epithelial layer cells with their uniquely formed pigment granules, the characteristic bi-lobed, cleaved nuclei from the outer nuclear layer, and nerve tissue likely from the outer plexiform layer of the retina. © 2013 American Society for Veterinary Clinical Pathology.

Malignancies and infection due to the human immunodeficiency virus. Are these emerging diseases?

PubMed

Valencia Ortega, M E

2018-04-01

Since the start of the human immunodeficiency virus (HIV) epidemic, tumour disease among patients has been significant. The collection of malignancies can be divided primarily into 2 groups: those associated with HIV (all of which are related to viral diseases) and those not associated with HIV (only some of which are associated with viral diseases). The origin of these malignancies is multifactorial, and the main causes that have led to an increase in tumour disease are immunosuppression, coinfection with oncogenic viruses and life prolongation secondary to the use of antiretroviral therapy. Establishing the general characteristics of the undiagnosed AIDS tumours is difficult, mainly because they are a highly heterogeneous group formed by malignancies of a diverse nature. The treatments do not differ from those used in the general population, although the management can be more difficult due to the late diagnosis, drug interactions and associated comorbidities. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.

Spot Scanning-Based Proton Therapy for Intracranial Meningioma: Long-Term Results From the Paul Scherrer Institute

DOE Office of Scientific and Technical Information (OSTI.GOV)

Weber, Damien C., E-mail: damien.weber@unige.ch; Schneider, Ralf; Goitein, Gudrun

2012-07-01

Background: To assess the long-term clinical results of spot scanning proton therapy (PT) in the treatment of intracranial meningiomas. Patients and Methods: Thirty-nine patients with meningioma (histologically proven 34/39) were treated with PT between July 1997 and January 2010. Thirty-two (82.1%) patients were treated as primary treatment (exclusive PT, n = 8; postoperative PT, n = 24). Mean age was 48.3 {+-} 17.9 years and 32 (82.1%) patients had skull base lesions. For patients undergoing surgery, 24 patients had a diagnosis of World Health Organization (WHO) Grade I and 10 of a WHO Grade II/III meningioma, respectively. The female-to-male ratiomore » was 3.3. The median administered dose was 56.0 Gy (relative biologic effectiveness [RBE]) (range, 52.2-66.6) at 1.8-2.0 Gy (RBE) per fraction. Gross tumor volume (GTV) ranged from 0.76 to 546.5 cm{sup 3} (median, 21.5). Late toxicity was assessed according to Common Terminology Criteria for Adverse Events version 3.0. Mean follow-up time was 62.0 months and all patients were followed for >6 months. Results: Six patients presented with tumor recurrence and 6 patients died during follow-up, of which 4 of tumor progression. Five-year actuarial local control and overall survival rates were 84.8% and 81.8%, respectively, for the entire cohort and 100% for benign histology. Cumulative 5-year Grade {>=}3 late toxicity-free survival was 84.5%. On univariate analysis, LC was negatively influenced by WHO grade (p = 0.001), GTV (p = 0.013), and male gender (p = 0.058). Conclusions: PT is a safe and effective treatment for patients with untreated, recurrent, or incompletely resected intracranial meningiomas. WHO grade and tumor volume was an adverse prognostic factor for local control.« less

Radiosurgery for Para-IAC Meningiomas: The Effect of Radiation Dose to the Cochlea on Hearing Outcome

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kim, Young-Hoon; Department of Neurosurgery, Seoul National University College of Medicine, Seoul; Kim, Dong Gyu, E-mail: gknife@plaza.snu.ac.kr

2012-11-01

Purpose: This study was performed to assess the radiosurgical results of meningiomas extending into the internal acoustic canal (para-IAC meningiomas), with a particular focus on the effect of radiation dose to the cochlea on hearing outcome. Methods and Materials: A total of 50 patients who underwent radiosurgery for para-IAC meningiomas between 1998 and 2009, which were followed for 2 years, were enrolled. The mean age was 55.8 years (range, 15-75). The mean tumor volume was 6.1 cm{sup 3} (range, 1.0-19.0), the mean tumor length in the IAC was 6.9 mm (range, 1.3-13.3), and the mean prescribed marginal dose was 13.1more » Gy (range, 10-15) at an isodose line of 50%. The mean follow-up duration was 46 months (range, 24-122). Results: Eight (16.0%) patients had nonserviceable hearing at the time of surgery. At the last follow-up, the tumor control rate was 94%; unchanged in 17 patients, decreased in 30 patients, and increased in 3 patients. Among 42 patients with serviceable hearing at the time of radiosurgery, it was preserved in 41 (97.6%) patients at the last follow-up. The maximal and mean radiation doses to the cochleae of these 41 patients were 5.8 Gy {+-} 0.3 (range, 3.1-11.5) and 4.3 Gy {+-} 0.2 (range, 2.2-7.5), respectively. The maximal dose to the cochlea of the patient who lost hearing after radiosurgery was 4.7 Gy. Conclusions: The radiation dose to the cochlea may have the minimal toxic effect on the hearing outcome in patients who undergo radiosurgery for para-IAC meningiomas.« less

Expression patterns of nicotinamide phosphoribosyltransferase and nicotinic acid phosphoribosyltransferase in human malignant lymphomas.

PubMed

Olesen, Uffe Høgh; Hastrup, Nina; Sehested, Maxwell

2011-04-01

The purpose of the study was to determine in human malignant lymphomas the expression patterns of nicotinamide phosphoribosyltransferase (NAMPT) and nicotinic acid phosphoribosyltransferase (NAPRT), the primary, rate-limiting enzymes in the synthesis of NAD+. NAMPT is a potential biomarker for sensitivity to NAMPT inhibitors and NAPRT is a biomarker for the use of nicotinic acid as a chemoprotectant in treatment with NAMPT inhibitors. The NAMPT inhibitor, APO866, is currently in clinical phase II trials in lymphomas. The expression of NAMPT and NAPRT was investigated in 53 samples of malignant lymphomas (diffuse large B-cell lymphoma, follicular B-cell lymphoma, Hodgkin's lymphoma and peripheral T-cell lymphoma). The expression of NAMPT was generally high in the more aggressive malignant lymphomas, with >80% strong expression, whereas the expression in the more indolent follicular lymphoma (FL) was significantly lower (>75% moderate or low expression, p = 0.0002). NAMPT was very highly expressed in Hodgkin Reed-Sternberg cells in Hodgkin's lymphoma. NAPRT expression was more varied (p > 0.0001) with 30-50% low expression except for Hodgkin's lymphoma where 85% displayed low expression (p = 0.0024). In conclusion, FL are a promising target for NAMPT inhibitors whereas substantial subsets of malignant lymphomas especially in Hodgkin lymphoma may be suitable for a combination treatment with nicotinic acid and NAMPT inhibitors. © 2011 The Authors. APMIS © 2011 APMIS.

Diagnosis and Management of Hereditary Meningioma and Vestibular Schwannoma.

PubMed

Shaw, Adam

2016-01-01

Bilateral vestibular schwannomata and meningiomata are the tumours most commonly associated with neurofibromatosis type II (NF2). These tumours may also be seen in patients with schwannomatosis and familial meningioma, but these phenotypes are usually easy to distinguish. The main diagnostic challenge when managing these tumours is distinguishing between sporadic disease which carries low risk of subsequent tumours or NF2 with its associated morbidities and reduced life expectancy. This chapter outlines some of the diagnostic and management considerations along with associated evidence.

Methylation of Werner syndrome protein is associated with the occurrence and development of invasive meningioma via the regulation of Myc and p53 expression.

PubMed

Li, Puxian; Hao, Shuyu; Bi, Zhiyong; Zhang, Junting; Wu, Zhen; Ren, Xiaohui

2015-08-01

The aim of the present study was to investigate the positive rate of Werner syndrome protein (WRN) methylation in meningioma patients, and further assess the association between WRN methylation and the occurrence of meningioma. A total of 56 consecutive meningioma patients and 26 healthy individuals were enrolled in the study. A methylation-specific polymerase chain reaction assay was performed to detect the positive rate of WRN methylation in the peripheral blood and tissue samples collected from the recruited subjects. In addition, western blot analysis was performed to determine the protein expression levels of WRN, Myc and p53 in the peripheral blood and tissue samples. The positive rate of WRN methylation in the peripheral blood of the meningioma group was increased when compared with the control group (P<0.05). In addition, the protein expression levels of WRN were significantly decreased in the peripheral blood and tissue samples collected from the individuals with a positive WRN methylation status (P<0.05), as compared with the samples without WRN methylation. Furthermore, the protein expression levels of Myc and p53 were increased in the peripheral blood and tissue samples that exhibited positive WRN methylation when compared with those without WRN methylation (P<0.05). Therefore, WRN methylation was demonstrated to be associated with the occurrence and development of invasive meningioma, possibly through the regulation of Myc and p53 expression.

Case-control study of the association between malignant brain tumours diagnosed between 2007 and 2009 and mobile and cordless phone use

PubMed Central

HARDELL, LENNART; CARLBERG, MICHAEL; SÖDERQVIST, FREDRIK; MILD, KJELL HANSSON

2013-01-01

Previous studies have shown a consistent association between long-term use of mobile and cordless phones and glioma and acoustic neuroma, but not for meningioma. When used these phones emit radiofrequency electromagnetic fields (RF-EMFs) and the brain is the main target organ for the hand-held phone. The International Agency for Research on Cancer (IARC) classified in May, 2011 RF-EMF as a group 2B, i.e. a ‘possible’ human carcinogen. The aim of this study was to further explore the relationship between especially long-term (>10 years) use of wireless phones and the development of malignant brain tumours. We conducted a new case-control study of brain tumour cases of both genders aged 18–75 years and diagnosed during 2007–2009. One population-based control matched on gender and age (within 5 years) was used to each case. Here, we report on malignant cases including all available controls. Exposures on e.g. use of mobile phones and cordless phones were assessed by a self-administered questionnaire. Unconditional logistic regression analysis was performed, adjusting for age, gender, year of diagnosis and socio-economic index using the whole control sample. Of the cases with a malignant brain tumour, 87% (n=593) participated, and 85% (n=1,368) of controls in the whole study answered the questionnaire. The odds ratio (OR) for mobile phone use of the analogue type was 1.8, 95% confidence interval (CI)=1.04–3.3, increasing with >25 years of latency (time since first exposure) to an OR=3.3, 95% CI=1.6–6.9. Digital 2G mobile phone use rendered an OR=1.6, 95% CI=0.996–2.7, increasing with latency >15–20 years to an OR=2.1, 95% CI=1.2–3.6. The results for cordless phone use were OR=1.7, 95% CI=1.1–2.9, and, for latency of 15–20 years, the OR=2.1, 95% CI=1.2–3.8. Few participants had used a cordless phone for >20–25 years. Digital type of wireless phones (2G and 3G mobile phones, cordless phones) gave increased risk with latency >1–5 years, then a

Case-control study of the association between malignant brain tumours diagnosed between 2007 and 2009 and mobile and cordless phone use.

PubMed

Hardell, Lennart; Carlberg, Michael; Söderqvist, Fredrik; Mild, Kjell Hansson

2013-12-01

Previous studies have shown a consistent association between long-term use of mobile and cordless phones and glioma and acoustic neuroma, but not for meningioma. When used these phones emit radiofrequency electromagnetic fields (RF-EMFs) and the brain is the main target organ for the handheld phone. The International Agency for Research on Cancer (IARC) classified in May, 2011 RF-EMF as a group 2B, i.e. a 'possible' human carcinogen. The aim of this study was to further explore the relationship between especially long-term (>10 years) use of wireless phones and the development of malignant brain tumours. We conducted a new case-control study of brain tumour cases of both genders aged 18-75 years and diagnosed during 2007-2009. One population-based control matched on gender and age (within 5 years) was used to each case. Here, we report on malignant cases including all available controls. Exposures on e.g. use of mobile phones and cordless phones were assessed by a self-administered questionnaire. Unconditional logistic regression analysis was performed, adjusting for age, gender, year of diagnosis and socio-economic index using the whole control sample. Of the cases with a malignant brain tumour, 87% (n=593) participated, and 85% (n=1,368) of controls in the whole study answered the questionnaire. The odds ratio (OR) for mobile phone use of the analogue type was 1.8, 95% confidence interval (CI)=1.04‑3.3, increasing with >25 years of latency (time since first exposure) to an OR=3.3, 95% CI=1.6-6.9. Digital 2G mobile phone use rendered an OR=1.6, 95% CI=0.996-2.7, increasing with latency >15-20 years to an OR=2.1, 95% CI=1.2-3.6. The results for cordless phone use were OR=1.7, 95% CI=1.1-2.9, and, for latency of 15-20 years, the OR=2.1, 95% CI=1.2-3.8. Few participants had used a cordless phone for >20-25 years. Digital type of wireless phones (2G and 3G mobile phones, cordless phones) gave increased risk with latency >1-5 years, then a lower risk in the following

Phase II study of Gleevec® plus hydroxyurea (HU) in adults with progressive or recurrent meningioma.

PubMed

Reardon, David A; Norden, Andrew D; Desjardins, Annick; Vredenburgh, James J; Herndon, James E; Coan, April; Sampson, John H; Gururangan, Sridharan; Peters, Katherine B; McLendon, Roger E; Norfleet, Julie A; Lipp, Eric S; Drappatz, Jan; Wen, Patrick Y; Friedman, Henry S

2012-01-01

We prospectively evaluated the efficacy and safety of imatinib plus hydroxyurea in patients with progressive/recurrent meningioma. A total of 21 patients with progressive/recurrent meningioma were enrolled in this dual center, single-arm, phase II trial. All patients received 500 mg of hydroxyurea twice a day. Imatinib was administered at 400 mg/day for patients not on CYP3A enzyme inducing anti-epileptic drugs (EIAEDs) and at 500 mg twice a day for patients on EIAEDs. The primary endpoint was progression-free survival at 6 months (PFS-6) and secondary endpoints were safety, radiographic response rate, and overall survival (OS). Best radiographic response was stable disease and was observed in 14 patients (67%). PFS-6 for all patients, those with grade I tumors (n = 8) and those with grade II or III tumors (n = 13) was 61.9, 87.5 and 46.2%, respectively. Patients with grade II or III tumors had poorer PFS and OS than those with grade I tumors, (P = 0.025 and P = 0.018) respectively. The only grade 3 or greater adverse event occurring in ≥ 10% of patients was anemia (10%). Imatinib plus hydroxyurea is well tolerated among patients with meningioma but has modest anti-tumor activity for this indication.

Phase II study of Gleevec® plus hydroxyurea (HU) in adults with progressive or recurrent meningioma

PubMed Central

Norden, Andrew D.; Desjardins, Annick; Vredenburgh, James J.; Herndon, James E.; Coan, April; Sampson, John H.; Gururangan, Sridharan; Peters, Katherine B.; McLendon, Roger E.; Norfleet, Julie A.; Lipp, Eric S.; Drappatz, Jan; Wen, Patrick Y.; Friedman, Henry S.

2011-01-01

We prospectively evaluated the efficacy and safety of imatinib plus hydroxyurea in patients with progressive/recurrent meningioma. A total of 21 patients with progressive/recurrent meningioma were enrolled in this dual center, single-arm, phase II trial. All patients received 500 mg of hydroxyurea twice a day. Imatinib was administered at 400 mg/day for patients not on CYP3A enzyme inducing anti-epileptic drugs (EIAEDs) and at 500 mg twice a day for patients on EIAEDs. The primary endpoint was progression-free survival at 6 months (PFS-6) and secondary endpoints were safety, radiographic response rate, and overall survival (OS). Best radiographic response was stable disease and was observed in 14 patients (67%). PFS-6 for all patients, those with grade I tumors (n = 8) and those with grade II or III tumors (n = 13) was 61.9, 87.5 and 46.2%, respectively. Patients with grade II or III tumors had poorer PFS and OS than those with grade I tumors, (P = 0.025 and P = 0.018) respectively. The only grade 3 or greater adverse event occurring in ≥10% of patients was anemia (10%). Imatinib plus hydroxyurea is well tolerated among patients with meningioma but has modest anti-tumor activity for this indication. PMID:21938530

Hypofractionated high-energy proton-beam irradiation is an alternative treatment for WHO grade I meningiomas.

PubMed

Vlachogiannis, Pavlos; Gudjonsson, Olafur; Montelius, Anders; Grusell, Erik; Isacsson, Ulf; Nilsson, Kristina; Blomquist, Erik

2017-12-01

Radiation treatment is commonly employed in the treatment of meningiomas. The aim of this study was to evaluate the effectiveness and safety of hypofractionated high-energy proton therapy as adjuvant or primary treatment for WHO grade I meningiomas. A total of 170 patients who received irradiation with protons for grade I meningiomas between 1994 and 2007 were included in the study. The majority of the tumours were located at the skull base (n = 155). Eighty-four patients were treated post subtotal resection, 42 at tumour relapse and 44 with upfront radiotherapy after diagnosis based on the typical radiological image. Irradiation was given in a hypofractionated fashion (3-8 fractions, usually 5 or 6 Gy) with a mean dose of 21.9 Gy (range, 14-46 Gy). All patients were planned for follow-up with clinical controls and magnetic resonance imaging scans at 6 months and 1, 2, 3, 5, 7 and 10 years after treatment. The median follow-up time was 84 months. Age, gender, tumour location, Simpson resection grade and target volume were assessed as possible prognostic factors for post-irradiation tumour progression and radiation related complications. The actuarial 5- and 10-year progression-free survival rates were 93% and 85% respectively. Overall mortality rate was 13.5%, while disease-specific mortality was 1.7% (3/170 patients). Older patients and patients with tumours located in the middle cranial fossa had a lower risk for tumour progression. Radiation-related complications were seen in 16 patients (9.4%), with pituitary insufficiency being the most common. Tumour location in the anterior cranial fossa was the only factor that significantly increased the risk of complications. Hypofractionated proton-beam radiation therapy may be used particularly in the treatment of larger World Health Organisation grade I meningiomas not amenable to total surgical resection. Treatment is associated with high rates of long-term tumour growth control and acceptable risk for

Second Malignant Neoplasms After Treatment of Childhood Acute Lymphoblastic Leukemia

PubMed Central

Schmiegelow, Kjeld; Levinsen, Mette Frandsen; Attarbaschi, Andishe; Baruchel, Andre; Devidas, Meenakshi; Escherich, Gabriele; Gibson, Brenda; Heydrich, Christiane; Horibe, Keizo; Ishida, Yasushi; Liang, Der-Cherng; Locatelli, Franco; Michel, Gérard; Pieters, Rob; Piette, Caroline; Pui, Ching-Hon; Raimondi, Susana; Silverman, Lewis; Stanulla, Martin; Stark, Batia; Winick, Naomi; Valsecchi, Maria Grazia

2013-01-01

Purpose Second malignant neoplasms (SMNs) after diagnosis of childhood acute lymphoblastic leukemia (ALL) are rare events. Patients and Methods We analyzed data on risk factors and outcomes of 642 children with SMNs occurring after treatment for ALL from 18 collaborative study groups between 1980 and 2007. Results Acute myeloid leukemia (AML; n = 186), myelodysplastic syndrome (MDS; n = 69), and nonmeningioma brain tumor (n = 116) were the most common types of SMNs and had the poorest outcome (5-year survival rate, 18.1% ± 2.9%, 31.1% ± 6.2%, and 18.3% ± 3.8%, respectively). Five-year survival estimates for AML were 11.2% ± 2.9% for 125 patients diagnosed before 2000 and 34.1% ± 6.3% for 61 patients diagnosed after 2000 (P < .001); 5-year survival estimates for MDS were 17.1% ± 6.4% (n = 36) and 48.2% ± 10.6% (n = 33; P = .005). Allogeneic stem-cell transplantation failed to improve outcome of secondary myeloid malignancies after adjusting for waiting time to transplantation. Five-year survival rates were above 90% for patients with meningioma, Hodgkin lymphoma, thyroid carcinoma, basal cell carcinoma, and parotid gland tumor, and 68.5% ± 6.4% for those with non-Hodgkin lymphoma. Eighty-nine percent of patients with brain tumors had received cranial irradiation. Solid tumors were associated with cyclophosphamide exposure, and myeloid malignancy was associated with topoisomerase II inhibitors and starting doses of methotrexate of at least 25 mg/m2 per week and mercaptopurine of at least 75 mg/m2 per day. Myeloid malignancies with monosomy 7/5q− were associated with high hyperdiploid ALL karyotypes, whereas 11q23/MLL-rearranged AML or MDS was associated with ALL harboring translocations of t(9;22), t(4;11), t(1;19), and t(12;21) (P = .03). Conclusion SMNs, except for brain tumors, AML, and MDS, have outcomes similar to their primary counterparts. PMID:23690411

Loss of Canonical Smad4 Signaling Promotes KRAS Driven Malignant Transformation of Human Pancreatic Duct Epithelial Cells and Metastasis

PubMed Central

Leung, Lisa; Radulovich, Nikolina; Zhu, Chang-Qi; Wang, Dennis; To, Christine; Ibrahimov, Emin; Tsao, Ming-Sound

2013-01-01

Pancreatic ductal adenocarcinoma (PDAC) is the fourth most common cause of cancer death in North America. Activating KRAS mutations and Smad4 loss occur in approximately 90% and 55% of PDAC, respectively. While their roles in the early stages of PDAC development have been confirmed in genetically modified mouse models, their roles in the multistep malignant transformation of human pancreatic duct cells have not been directly demonstrated. Here, we report that Smad4 represents a barrier in KRAS-mediated malignant transformation of the near normal immortalized human pancreatic duct epithelial (HPDE) cell line model. Marked Smad4 downregulation by shRNA in KRAS G12V expressing HPDE cells failed to cause tumorigenic transformation. However, KRAS-mediated malignant transformation occurred in a new HPDE-TGF-β resistant (TβR) cell line that completely lacks Smad4 protein expression and is resistant to the mito-inhibitory activity of TGF-β. This transformation resulted in tumor formation and development of metastatic phenotype when the cells were implanted orthotopically into the mouse pancreas. Smad4 restoration re-established TGF-β sensitivity, markedly increased tumor latency by promoting apoptosis, and decreased metastatic potential. These results directly establish the critical combination of the KRAS oncogene and complete Smad4 inactivation in the multi-stage malignant transformation and metastatic progression of normal human HPDE cells. PMID:24386371

Content-based analysis of Ki-67 stained meningioma specimens for automatic hot-spot selection.

PubMed

Swiderska-Chadaj, Zaneta; Markiewicz, Tomasz; Grala, Bartlomiej; Lorent, Malgorzata

2016-10-07

Hot-spot based examination of immunohistochemically stained histological specimens is one of the most important procedures in pathomorphological practice. The development of image acquisition equipment and computational units allows for the automation of this process. Moreover, a lot of possible technical problems occur in everyday histological material, which increases the complexity of the problem. Thus, a full context-based analysis of histological specimens is also needed in the quantification of immunohistochemically stained specimens. One of the most important reactions is the Ki-67 proliferation marker in meningiomas, the most frequent intracranial tumour. The aim of our study is to propose a context-based analysis of Ki-67 stained specimens of meningiomas for automatic selection of hot-spots. The proposed solution is based on textural analysis, mathematical morphology, feature ranking and classification, as well as on the proposed hot-spot gradual extinction algorithm to allow for the proper detection of a set of hot-spot fields. The designed whole slide image processing scheme eliminates such artifacts as hemorrhages, folds or stained vessels from the region of interest. To validate automatic results, a set of 104 meningioma specimens were selected and twenty hot-spots inside them were identified independently by two experts. The Spearman rho correlation coefficient was used to compare the results which were also analyzed with the help of a Bland-Altman plot. The results show that most of the cases (84) were automatically examined properly with two fields of view with a technical problem at the very most. Next, 13 had three such fields, and only seven specimens did not meet the requirement for the automatic examination. Generally, the Automatic System identifies hot-spot areas, especially their maximum points, better. Analysis of the results confirms the very high concordance between an automatic Ki-67 examination and the expert's results, with a Spearman

Pterional approach versus unilateral frontal approach on tuberculum sellae meningioma: Single centre experiences

PubMed Central

Arifin, Muhammad Zafrullah; Mardjono, Ignatius; Sidabutar, Roland; Wirjomartani, Beny Atmadja; Faried, Ahmad

2012-01-01

Introduction: Tuberculum Sellae Meningioma is one of the most challenging surgeries among neurosurgeons. Many approaches have been established in the effort of removing the tumor and some of them are supported by an advanced neurosurgical technology. In this study, we aim to compare the efficacy of the two most common approaches, the pterional and the unilateral frontal. Materials and Methods: This was a restrospective study that aimed to observe the efficacy of the two most common approaches used in our center, the pterional and the unilateral frontal, in resecting the tuberculum sellae meningioma, which was held in Dr. Hasan Sadikin General Hospital, Bandung, from July 2007-July 2010. Twenty patients were enrolled with half of them operated by the pterional approach and the rest by unilateral frontal approach. We evaluated six parameters: tumor size, degree of tumor removal, surgery duration, post-operative cerebral edema, patients' outcome, and length of stay, which were evaluated to take measure of the efficacy of each procedure. Results: We found that the pterional approach gave more advantages than the unilateral frontal. Total tumor removal, especially in tumor size ≥ 3 cm was achieved in a greater number of subjects in the pterional (P<0.023). Other advantages of the pterional compared to the unilateral frontal were a shorter surgical duration (P=0.024), shorter length of stay (P=0.009) and less frequency of post-operative cerebral edema incidence (P=0.023). Conclusion: According to our facilities and conditions, it seems that the pterional approach have more advantages than the unilateral frontal approach in tuberculum sellae meningioma surgery. PMID:22639687

[Dynamic retraction microneurosurgery for the treatment of medial tentorial meningiomas].

PubMed

Du, W; Zhong, D; Lü, D; Li, J; Huang, H Y; Yang, J; Wu, Y T; Xia, H J; Tang, W Y; Sun, X C

2018-05-08

Objective: To investigate the effectiveness and clinical significance of dynamic retraction microneurosurgery for the treatment of medial tentorial meningiomas. Methods: From January 2011 to December 2016, a cohort of 28 patients with medial tentorial meningiomas were treated by microneurosurgery at the First Affiliated Hospital of Chongqing Medical University. Patients who treated intraoperatively with dynamic retraction surgery from January 2014 to December 2016 were assigned into dynamic retraction group, and those with fixed retractors intraoperatively from January 2011 to December 2013 were assigned into retractor group. The surgical approaches tailored in our patients were based on predominant direction of tumor extension. The extent of tumor resection was scored according to the Simpson's classification scale. Comparisons of tumor size, operation time, hospitalization time, retraction-related injury, tumor Simpson resection grade and Karnofsky Performance Scale(KPS) score six months after surgery were also made between two groups. Results: A total of 12 patients(retractor group) were treated with the use of self-retaining brain retractors intraoperatively and dynamic retraction surgical procedure was performed intraoperatively in 16 patients(dynamic retraction group). The difference between two groups with regard to sex, age, tumor size, operation time and tumor Simpson resection grade was not statistically significant(all P >0.05). The mean duration of hospital time was shorter in the dynamic retraction group than that in the retractor group(18.3 d±1.8 d vs 20.2 d±1.3 d, P =0.004). The dynamic retraction group had lower incidence of retraction-related injury compared with the retractor group(1/16 vs 6/12), P =0.022]. The dynamic retraction group had better neurological recovery rate with KPS >80 evaluated six months after surgery compared with the retractor group(14/16 vs 5/12, P =0.017). Conclusions: Dynamic retraction microneurosurgery for the treatment

Immunohistochemical analysis of cyclooxygenase-2 and brain fatty acid binding protein expression in grades I-II meningiomas: correlation with tumor grade and clinical outcome after radiotherapy.

PubMed

Kang, Hyun-Cheol; Kim, Il Han; Park, Charn Il; Park, Sung-Hye

2014-10-01

This study was done to evaluate the association of cyclooxygenase 2 (COX-2) and brain fatty acid binding protein (BFABP) with tumor grade and outcome of grades I-II meningiomas treated with radiotherapy. From 1996 to 2008, 40 patients with intracranial grades I-II meningiomas were treated with radiotherapy. Immunohistochemical staining for COX-2 and BFABP were performed on formalin-fixed paraffin-embedded tissues. COX-2 expression was significantly associated with BFABP status and both COX-2 (P < 0.01) and BFABP (P = 0.01) expression were stronger in the grade II meningiomas than in grade I tumors. Among the clinicopathologic factors, age and COX-2 status were prognostic in progression-free survival. Patients with moderate or strong COX-2 expression had worse outcome than those with negative or weak COX-2 expression (P = 0.03) after controlling for potential confounders. Our results suggest that the molecular biomarker COX-2 has prognostic significance in intracranial grades I-II meningiomas following radiotherapy. © 2014 Japanese Society of Neuropathology.

Microsurgical Resection of Lateral Tuberculum Sellae Meningioma: Operative Video.

PubMed

Cândido, Duarte N C; Nakashima, Paulo E H; de Oliveira, Jean Gonçalves; Borba, Luis A B

2018-02-01

Tuberculum Sellae Meningiomas (TSMs) are lesions dramatically related to the optic apparatus once the principal clinical complain remains on visual alterations. This is the main picture on decision making to evaluate the best time, risk-benefit, and surgical approaches to the patient treatment. In this video, we present a 65 years old female with 30 days complaint of unilateral (right) complete blindness and complete impaired right eye field test. On physical examination, there were normal pupillary function to light tests. The scans demonstrated the presence of a TSM mostly related to the right optic nerve and encasing it altogether with the right internal carotid artery. Promptly, surgery was addressed using a modified one piece cranio-orbital-zygomatic approach with extra-dural anterior clinoidectomy, as this is the procedure of choice of the senior author (LB), with easy access to decompression of the optic canal and nerve. As demonstrated on the video, the optic nerve was encased by the tumor and pushed upwards against the falciform ligament. Complete resection and decompression was established with step by step dissection, starting unroofing the optic canal, opening the ligament and finally with carefully tumor debulking. Pathology demonstrated a grade one meningioma. The patient improved remarkably her visual acuity and visual field tests on the postoperative period, emphasizing the importance of early treatment for nerve function outcome. The link to the video can be found at: https://youtu.be/pALZqDUkltQ .

The role of magnetic resonance diffusion-weighted imaging and three-dimensional arterial spin labelling perfusion imaging in the differentiation of parasellar meningioma and cavernous haemangioma.

PubMed

Xiao, Hua-Feng; Lou, Xin; Liu, Meng-Yu; Wang, Yu-Lin; Wang, Yan; Chen, Zhi-Ye; Shi, Kai-Ning; Ma, Lin

2014-08-01

To evaluate the diagnostic value of magnetic resonance diffusion-weighted imaging (DWI) and three-dimensional arterial spin labelling perfusion imaging (3D-ASL) in distinguishing cavernous haemangioma from parasellar meningioma, using histological data as a reference standard. Patients with parasellar meningioma or parasellar cavernous haemangioma underwent conventional T1- and T2-weighted magnetic resonance imaging (MRI) followed by DWI and 3D-ASL using a 3.0 Tesla MRI. The minimum apparent diffusion coefficient (minADC) from DWI and the maximal normalized cerebral blood flow (nCBF) from 3D-ASL were measured in each tumour. Diagnosis was confirmed by histology. MinADC was significantly lower and nCBF significantly higher in meningioma (n = 19) than cavernous haemangioma (n = 15). There was a significant negative correlation between minADC and nCBF (r = -0.605). DWI and 3D-ASL are useful in differentiating cavernous haemangiomas from parasellar meningiomas, particularly in situations when the appearance on conventional MRI sequences is otherwise ambiguous. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Detailed anatomy knowledge: first step to approach petroclival meningiomas through the petrous apex. Anatomy lab experience and surgical series.

PubMed

Altieri, Roberto; Sameshima, Tetsuro; Pacca, Paolo; Crobeddu, Emanuela; Garbossa, Diego; Ducati, Alessandro; Zenga, Francesco

2017-04-01

Petroclival meningiomas are a challenge for neurosurgeons due to the complex anatomy of the region that is rich of vessels and nerves. A perfect and detailed knowledge of the anatomy is very demanding in neurosurgery, especially in skull base surgery. The authors describe the microsurgical anatomy to perform an anterior petrosectomy based on their anatomical and surgical experience and perform a literature review. The temporal bone is the most complex and fascinating bone of skull base. The apex is located in the angle between the greater wing of the sphenoid and the occipital bone. Removing the petrous apex exposes the clivus. The approach directed through the temporal bone in this anatomical area is referred to as an anterior petrosectomy. The area that must be drilled is the rhomboid fossa that is defined by the Kawase, premeatal, and postmeatal triangles. In Division of Neurosurgery - University of Turin, 130 patients, from August 2013 to September 2015, underwent surgical resection of intracranial meningiomas. In this group, we have operated 7 PCMs and 5 of these were approached performing an anterior petrosectomy with good results. In our conclusions, we feel that this surgery require an advanced knowledge of human anatomy and a specialized training in interpretation of radiological and microsurgical anatomy both in the dissection lab and in the operating room.

Comparative oncology: what dogs and other species can teach us about humans with cancer

PubMed Central

Schiffman, Joshua D.; Breen, Matthew

2015-01-01

Over 1.66 million humans (approx. 500/100 000 population rate) and over 4.2 million dogs (approx. 5300/100 000 population rate) are diagnosed with cancer annually in the USA. The interdisciplinary field of comparative oncology offers a unique and strong opportunity to learn more about universal cancer risk and development through epidemiology, genetic and genomic investigations. Working across species, researchers from human and veterinary medicine can combine scientific findings to understand more quickly the origins of cancer and translate these findings to novel therapies to benefit both human and animals. This review begins with the genetic origins of canines and their advantage in cancer research. We next focus on recent findings in comparative oncology related to inherited, or genetic, risk for tumour development. We then detail the somatic, or genomic, changes within tumours and the similarities between species. The shared cancers between humans and dogs that we discuss include sarcoma (osteosarcoma, soft tissue sarcoma, histiocytic sarcoma, hemangiosarcoma), haematological malignancies (lymphoma, leukaemia), bladder cancer, intracranial neoplasms (meningioma, glioma) and melanoma. Tumour risk in other animal species is also briefly discussed. As the field of genomics advances, we predict that comparative oncology will continue to benefit both humans and the animals that live among us. PMID:26056372

Coexistence of Radiation-Induced Meningioma and Moyamoya Syndrome 10 Years after Irradiation against Medulloblastoma: a Case Report.

PubMed

Han, Ji Yeon; Choi, Jung Won; Wang, Kyu Chang; Phi, Ji Hoon; Lee, Ji Yeoun; Chae, Jong Hee; Park, Sung Hye; Cheon, Jung Eun; Kim, Seung Ki

2017-11-01

Radiotherapy is one of the standard treatments for medulloblastoma. However, therapeutic central nervous system irradiation in children may carry delayed side effects, such as radiation-induced tumor and vasculopathy. Here, we report the first case of coexisting meningioma and moyamoya syndrome, presenting 10 years after radiotherapy for medulloblastoma. A 13-year-old boy presented with an enhancing mass at the cerebral falx on magnetic resonance imaging (MRI) after surgery, radiotherapy (30.6 Gy craniospinal axis, 19.8 Gy posterior fossa) and chemotherapy against medulloblastoma 10 years ago, previously. The second tumor was meningioma. On postoperative day 5, he complained of right-sided motor weakness, motor dysphasia, dysarthria, and dysphagia. MRI revealed acute cerebral infarction in the left frontal lobe and both basal ganglia. MR and cerebral angiography confirmed underlying moyamoya syndrome. Four months after the meningioma surgery, the patient presented with headaches, dysarthria, and dizziness. Indirect bypass surgery was performed. He has been free from headaches since one month after the surgery. For patients who received radiotherapy for medulloblastoma at a young age, clinicians should consider the possibility of the coexistence of several complications. Careful follow up for development of secondary tumor and delayed vasculopathy is required. © 2017 The Korean Academy of Medical Sciences.

[Formed visual hallucination after excision of the right temporo parietal cystic meningioma--a case report].

PubMed

Yoshimura, Masaki; Uchiyama, Yoshinori; Kaneko, Akira; Hayashi, Noriko; Yamanaka, Kazuhiro; Iwai, Yoshiyasu

2010-08-01

We report the case of a 64-year-old woman with cystic meningioma; this patients was otherwise healthy and experienced formed visual hallucinations after excision of the tumor. She experienced diplopia associated with metamorphopsia, which had persisted for 5 years only when she laid down and turned on her left side. After the excision of the convexity meningioma located in the right temporoparietal lobe, she experienced several types of formed visual hallucinations such as closet-like pictures, flowers sketched on stones, falling maple-like leaves, and moving or wriggling dwarves. She was alert and her visual field was normal; further, she did not experience delirium or seizures. She experienced these hallucinations only when she closed her eyes; these hallucinations persisted for 3 days after the operation. The patient illustrated her observations with beautiful sketches, and the mechanism of visual hallucinations was studied.

The activation of human endogenous retrovirus K (HERV-K) is implicated in melanoma cell malignant transformation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Serafino, A.; Balestrieri, E.; Pierimarchi, P.

2009-03-10

Melanoma development is a multi-step process arising from a series of genetic and epigenetic events. Although the sequential stages involved in progression from melanocytes to malignant melanoma are clearly defined, our current understanding of the mechanisms leading to melanoma onset is still incomplete. Growing evidence show that the activation of endogenous retroviral sequences might be involved in transformation of melanocytes as well as in the increased ability of melanoma cells to escape immune surveillance. Here we show that human melanoma cells in vitro undergo a transition from adherent to a more malignant, non-adherent phenotype when exposed to stress conditions. Melanoma-derivedmore » non-adherent cells are characterized by an increased proliferative potential and a decreased expression of both HLA class I molecules and Melan-A/MART-1 antigen, similarly to highly malignant cells. These phenotypic and functional modifications are accompanied by the activation of human endogenous retrovirus K expression (HERV-K) and massive production of viral-like particles. Down-regulation of HERV-K expression by RNA interference prevents the transition from the adherent to the non-adherent growth phenotype in low serum. These results implicate HERV-K in at least some critical steps of melanoma progression.« less

Poly(ADP-ribose) polymerase-independent potentiation of nitrosourea cytotoxicity by 3-aminobenzamide in human malignant glioma cells.

PubMed

Winter, S; Weller, M

2000-06-16

Poly(ADP-ribose) polymerase is a zinc-finger DNA-binding protein that detects specifically DNA strand breaks generated by genotoxic agents and is thought to be involved in DNA repair. Here, we examined the effects of 3-aminobenzamide, a poly(ADP-ribose) polymerase inhibitor, on the chemosensitivity of human malignant glioma cells. 3-Aminobenzamide selectively potentiated the cytotoxicity of the nitrosoureas, nimustine, carmustine and lomustine in 10 of 12 human malignant glioma cell lines. In contrast, 3-aminobenzamide did not modulate the cytotoxic effects of doxorubicine, teniposide, vincristine, camptothecin or cytarabine. The nitrosoureas did not induce poly(ADP-ribose) polymerase activity in the glioma cells. Ectopic expression of truncated poly(ADP-ribose) polymerase containing the poly(ADP-ribose) polymerase DNA-binding domain, which acts as a dominant-negative mutant, in LN-18 or LN-229 cells did not alter the 3-aminobenzamide effect on nitrosourea-mediated cytotoxicity. Thus, 3-aminobenzamide may target another nicotinamide adenine dinucleotide (NAD)-requiring enzyme, but not poly(ADP-ribose) polymerase, when enhancing nitrosourea cytotoxicity in human malignant glioma cells. Carmustine cytotoxicity was associated with a G2/M arrest. Coexposure to carmustine and 3-aminobenzamide overcame this G2/M arrest in T98G cells, which are sensitized to carmustine by 3-aminobenzamide, but not in U251MG cells, which are refractory to 3-aminobenzamide-mediated sensitization to carmustine. Thus, 3-aminobenzamide-mediated sensitization to carmustine cytotoxicity may result from interference with the stable G2/M arrest response to carmustine in human glioma cells.

Day of Surgery Impacts Outcome: Rehabilitation Utilization on Hospital Length of Stay in Patients Undergoing Elective Meningioma Resection.

PubMed

Sarkiss, Christopher A; Papin, Joseph A; Yao, Amy; Lee, James; Sefcik, Roberta K; Oermann, Eric K; Gordon, Errol L; Post, Kalmon D; Bederson, Joshua B; Shrivastava, Raj K

2016-09-01

Meningiomas account for approximately one third of all brain tumors in the United States. In high-volume medical centers, the average length of stay (LOS) for a patient is 6.8 days compared with 8.8 days in low-volume centers with median total admission charges equaling approximately $55,000. To our knowledge, few studies have evaluated day of surgery and its effect on hospital LOS. Our primary goal was to analyze patient outcome as a direct result of surgical date, as well as to characterize the individual variables that may impact their hospital course, early access to rehabilitation, and long-term functional status. A retrospective database was generated for cranial meningioma patients who underwent elective surgical resection at our institution over a 3-year study period (2011-2014). Inclusion criteria included any patient who underwent elective meningioma resection and was discharged either home or to a rehabilitation facility with at least 6 months of follow-up. Exclusion criteria included any patient who was not discharged after resection (i.e., expired). Each patient's medical record was evaluated for a subset of demographics and clinical variables. Given that patients who undergo surgical resection of meningiomas have a national median LOS of 6 days, we subdivided the patients into 2 cohorts: early discharge (LOS < 3) and late discharge (LOS ≥ 3). Statistical analysis was performed using SPSS 21.0 to assess the significance of the results. We identified 139 (25 male, 114 female) meningioma patients who underwent surgical resection. Seventy of these patients had surgery during the early week (defined as Monday-Wednesday), and 69 had surgery in the later week (Thursday-Friday). The median age for both early and late groups was 58, and the median diameter of the tumor was 3.1 cm and 3.3 cm, respectively. Overall, 55% of the patients had public insurance and 43% had private insurance, with no significant variation between the early and late groups. The

Coexistence of neurofibroma and meningioma at exactly the same level of the cervical spine.

PubMed

Chen, Kai-Yuan; Wu, Jau-Ching; Lin, Shih-Cheih; Huang, Wen-Cheng; Cheng, Henrich

2014-11-01

We report a case of the coexistence of different spinal tumors at the same level of the cervical spine, without neurofibromatosis (NF), which was successfully treated with surgery. A 72-year-old female presented with right upper-limb clumsiness and weakness. Magnetic resonance imaging revealed an intradural, extramedullary tumor mass at the right C3-4 level with extradural extension into the intervertebral foramen. The extradural tumor was removed, and the pathology showed neurofibroma. After incision of the dura, the intradural tumor was removed, and was identified as meningioma in the pathological report. The patient did not meet the criteria of NF. Coexistence of neurofibroma and meningioma at exactly the same level of the spine without NF is extremely rare. Exploration of the intradural space may be necessary after resection of an extradural tumor if the surgical finding does not correlate well with the preoperative images. Copyright © 2014. Published by Elsevier Taiwan.

Microbiome and Malignancy

PubMed Central

Plottel, Claudia S.; Blaser, Martin J.

2011-01-01

Current knowledge is insufficient to explain why only a proportion of individuals exposed to environmental carcinogens or carrying a genetic predisposition to cancer develop disease. Clearly, other factors must be important and one such element that has recently received attention is the human microbiome, the residential microbes including Bacteria, Archaea, Eukaryotes, and viruses that colonize humans. Here, we review principles and paradigms of microbiome-related malignancy, as illustrated by three specific microbial-host interactions. We review the effects of the microbiota on local and adjacent-neoplasia, present the estrobolome model of distant effects, and discuss the complex interactions with a latent virus leading to malignancy. These are separate facets of a complex biology interfacing all the microbial species we harbor from birth onward toward early reproductive success and eventual senescence. PMID:22018233

Single-fraction Radiosurgery for Presumed Intracranial Meningiomas: Efficacy and Complications From a 22-Year Experience

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pollock, Bruce E., E-mail: pollock.bruce@mayo.edu; Department of Radiation Oncology, Mayo Clinic College of Medicine, Rochester, MN; Stafford, Scott L.

Purpose: To define the rate of tumor control and factors associated with radiation-related complications after single-fraction radiosurgery (SRS) for patients with imaging defined intracranial meningiomas. Materials and Methods: Retrospective review of 251 patients (192 women, 59 men) having SRS for imaging-defined intracranial meningiomas between 1990 and 2008. Excluded were patients with radiation-induced tumors, meningiomatosis, or neurofibromatosis. The mean patient age was 58.6 {+-} 13.4 years. The majority of tumors involved the skull base/tentorium (n = 210, 83.7%). The mean treatment volume was 7.7 {+-} 6.2 cm{sup 3}; the mean tumor margin dose was 15.8 {+-} 2.0 Gy. Follow-up (mean, 62.9more » {+-} 43.9 months) was censored at last evaluation (n = 224), death (n = 22), or tumor resection (n = 5). Results: No patient died from tumor progression or radiation-related complications. Tumor size decreased in 181 patients (72.1%) and was unchanged in 67 patients (26.7%). Three patients (1.2%) had in-field tumor progression noted at 28, 145, and 150 months, respectively. No patient had a marginal tumor progression. The 3- and 10-year local control rate was 99.4%. One patient had distant tumor progression at 105 months and underwent repeat SRS. Thirty-one patients (12.4%) had either temporary (n = 8, 3.2%) or permanent (n = 23, 9.2%) symptomatic radiation-related complications including cranial nerve deficits (n = 14), headaches (n = 5), hemiparesis (n = 5), new/worsened seizure (n = 4), cyst-formation (n = 1), hemifacial spasm (n = 1), and stroke (n = 1). The 1- and 5-year complication rates were 8.3% and 11.5%, respectively. Radiation-related complications were associated with convexity/falx tumors (HR = 2.8, 95% CI 1.3-6.1, p = 0.009) and increasing tumor volume (HR = 1.05, 95% CI 1.0-1.1, p = 0.04) on multivariate analysis. No patient developed a radiation-induced tumor. Conclusions: Single-fraction SRS at the used dose range provides a high rate of tumor

Relevancia de los grados de Simpson en la resección de meningiomas grado I

PubMed Central

Ajler, Pablo; Beltrame, Sofía; Massa, Daniela; Tramontano, Julian; Baccanelli, Matteo; Yampolsky, Claudio

2017-01-01

Resumen Objetivo: Comparar el porcentaje de recurrencias en pacientes con meningiomas grado I de la OMS sometidos a exéresis microquirúrgica. Introducción: En 1957 Simpson estandarizó 5 grados de resección quirúrgica para los meningiomas intracraneanos y el porcentaje de recurrencia relacionado con cada uno, estableciendo el paradigma de que la remoción agresiva de estos tumores junto con fragmentos durales y óseos era necesario para alcanzar la curación. Los avances principalmente en Resonancia Magnética, anatomía patológica y técnica microqurúrgica nos llevan a plantear la relevancia actual de dicha clasificación. Métodos: Se realizó una revisión retrospectiva de los pacientes operados de meningiomas grado I entre Febrero de 2006 y Diciembre de 2015. Se analizaron las imágenes pre y postoperatorias y la anatomía patológica. Las variables se relacionaron mediante un análisis estadístico multivariado estableciendo como estadísticamente significativo una P < 0.05. Resultados: No se objetivó una diferencia estadísticamente significativa entre el número de recidivas y el grado de resección tumoral según Simpson I, II, III o IV (P = 0,3117). Esto puede afirmarse para los grados Simpson I y II en donde el número de pacientes incluidos en la muestra (n) fue alto. Al analizar como factor de recurrencia la localización tumoral tampoco se encontró una diferencia significativa en cuanto al porcentaje de recidivas entre aquellos tumores localizados en la convexidad, base de cráneo y parasagitales (P = 0,2203). Conclusión: Para los meningiomas grado I la exéresis Simpson I no presenta diferencias significativas con la Simpson II en cuanto a la recurrencia tumoral, por lo que aumentar la morbilidad del procedimiento no tendría justificación. Un replanteo de la escala de resección debería idearse teniendo en cuenta la clasificación de la OMS. PMID:29142775

Withania somnifera Root Extract Has Potent Cytotoxic Effect against Human Malignant Melanoma Cells

PubMed Central

Halder, Babli; Singh, Shruti; Thakur, Suman S.

2015-01-01

In Ayurveda, Withania somnifera is commonly known as Ashwagandha, its roots are specifically used in medicinal and clinical applications. It possesses numerous therapeutic actions which include anti-inflammatory, sedative, hypnotic and narcotic. Extracts from this plant have been reported for its anticancer properties. In this study we evaluated for the first time, the cytotoxic effect of Withania root extract on human malignant melanoma A375 cells. The crude extract of Withania was tested for cytotoxicity against A375 cells by MTT assay. Cell morphology of treated A375 cells was visualized through phase contrast as well as fluorescence microscopy. Agarose gel electrophoresis was used to check DNA fragmentation of the crude extract treated cells. Crude extract of Withania root has the potency to reduce viable cell count in dose as well as time dependent manner. Morphological change of the A375 cells was also observed in treated groups in comparison to untreated or vehicle treated control. Apoptotic body and nuclear blebbing were observed in DAPI stained treated cells under fluorescence microscope. A ladder of fragmented DNA was noticed in treated cells. Thus it might be said that the crude water extract of Withania somnifera has potent cytotoxic effect on human malignant melanoma A375 cells. PMID:26334881

The Sodium Iodide Symporter (NIS) and Potential Regulators in Normal, Benign and Malignant Human Breast Tissue

PubMed Central

Ryan, James; Curran, Catherine E.; Hennessy, Emer; Newell, John; Morris, John C.; Kerin, Michael J.; Dwyer, Roisin M.

2011-01-01

Introduction The presence, relevance and regulation of the Sodium Iodide Symporter (NIS) in human mammary tissue remains poorly understood. This study aimed to quantify relative expression of NIS and putative regulators in human breast tissue, with relationships observed further investigated in vitro. Methods Human breast tissue specimens (malignant n = 75, normal n = 15, fibroadenoma n = 10) were analysed by RQ-PCR targeting NIS, receptors for retinoic acid (RARα, RARβ), oestrogen (ERα), thyroid hormones (THRα, THRβ), and also phosphoinositide-3-kinase (PI3K). Breast cancer cells were treated with Retinoic acid (ATRA), Estradiol and Thyroxine individually and in combination followed by analysis of changes in NIS expression. Results The lowest levels of NIS were detected in normal tissue (Mean(SEM) 0.70(0.12) Log10 Relative Quantity (RQ)) with significantly higher levels observed in fibroadenoma (1.69(0.21) Log10RQ, p<0.005) and malignant breast tissue (1.18(0.07) Log10RQ, p<0.05). Significant positive correlations were observed between human NIS and ERα (r = 0.22, p<0.05) and RARα (r = 0.29, p<0.005), with the strongest relationship observed between NIS and RARβ (r = 0.38, p<0.0001). An inverse relationship between NIS and PI3K expression was also observed (r = −0.21, p<0.05). In vitro, ATRA, Estradiol and Thyroxine individually stimulated significant increases in NIS expression (range 6–16 fold), while ATRA and Thyroxine combined caused the greatest increase (range 16–26 fold). Conclusion Although NIS expression is significantly higher in malignant compared to normal breast tissue, the highest level was detected in fibroadenoma. The data presented supports a role for retinoic acid and estradiol in mammary NIS regulation in vivo, and also highlights potential thyroidal regulation of mammary NIS mediated by thyroid hormones. PMID:21283523

[Embolization of the feeding artery of a meningioma with dangerous vascular anastomosis between the middle meningeal artery and the ophthalmic artery].

PubMed

Meguro, Toshinari; Tomita, Yusuke; Tanabe, Tomoyuki; Muraoka, Kenichiro; Terada, Kinya; Hirotsune, Nobuyuki; Nishino, Shigeki

2013-11-01

Preoperative embolization of intracranial meningioma has been applied to reduce intraoperative blood loss and to facilitate microsurgical removal of a tumor. It is well known that one of the reasons of the neurological risk of embolization is due to dangerous anastomosis between the extracranial and the intracranial arteries. One of the most known and dangerous case of anastomosis is between the middle meningeal artery to the ophthalmic artery. A 48-year-old woman underwent preoperative embolization of a large right middle cranial fossa meningioma. The right external carotid angiogram showed that the tumor was fed by the right middle meningeal artery and there was no branch to the right orbital region. The right internal carotid angiogram showed that the right ophthalmic artery originated from the right internal carotid artery and there was no branch to the tumor. The selective angiogram of the anterior branch of the middle meningeal artery disclosed the anastomosis to the right ophthalmic artery. Following embolization of the anterior branch of the middle meningeal artery, the patient underwent embolization of the main feeding branch of the meningioma. She successfully underwent surgical removal of the tumor without any blood transfusion and was discharged without neurological deficit. In addition, to avoid complication in embolization of the feeding artery of a skull base meningioma, clinicians must be aware of the dangerous anastomosis between the middle meningeal artery and the ophthalmic artery, even if conventional external and internal carotid angiograms do not show any anastomosis.

Sensitization of recombinant human tumor necrosis factor-related apoptosis-inducing ligand-resistant malignant melanomas by quercetin.

PubMed

Turner, Katherine A; Manouchehri, Jasmine M; Kalafatis, Michael

2018-03-28

Malignant melanoma is the most commonly diagnosed skin cancer associated with a high rate of metastasis. Low-stage melanoma is easily treated, but metastatic malignant melanoma is an extremely treatment-resistant malignancy with low survival rates. The application of recombinant human tumor necrosis factor-related apoptosis-inducing ligand (rhTRAIL) for the treatment of metastatic malignant melanoma holds considerable promise because of its selective proapoptotic activity towards cancer cells and not nontransformed cells. Unfortunately, the clinical utilization of rhTRAIL has been terminated due to the resistance of many cancer cells to undergo apoptosis in response to rhTRAIL. However, rhTRAIL-resistance can be abrogated through the cotreatment with compounds derived from 'Mother Nature' such as quercetin that can modulate cellular components responsible for rhTRAIL-resistance. Here, we show that rhTRAIL-resistant malignant melanomas are sensitized by quercetin. Quercetin action is manifested by the upregulation of rhTRAIL-binding receptors DR4 and DR5 on the surface of cancer cells and by increased rate of the proteasome-mediated degradation of the antiapoptotic protein FLIP. Our data provide for a new efficient and nontoxic treatment of malignant melanoma.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0/.

Multimodal optical analysis discriminates freshly extracted human sample of gliomas, metastases and meningiomas from their appropriate controls

NASA Astrophysics Data System (ADS)

Zanello, Marc; Poulon, Fanny; Pallud, Johan; Varlet, Pascale; Hamzeh, H.; Abi Lahoud, Georges; Andreiuolo, Felipe; Ibrahim, Ali; Pages, Mélanie; Chretien, Fabrice; di Rocco, Federico; Dezamis, Edouard; Nataf, François; Turak, Baris; Devaux, Bertrand; Abi Haidar, Darine

2017-02-01

Delineating tumor margins as accurately as possible is of primordial importance in surgical oncology: extent of resection is associated with survival but respect of healthy surrounding tissue is necessary for preserved quality of life. The real-time analysis of the endogeneous fluorescence signal of brain tissues is a promising tool for defining margins of brain tumors. The present study aims to demonstrate the feasibility of multimodal optical analysis to discriminate fresh samples of gliomas, metastases and meningiomas from their appropriate controls. Tumor samples were studied on an optical fibered endoscope using spectral and fluorescence lifetime analysis and then on a multimodal set-up for acquiring spectral, one and two-photon fluorescence images, second harmonic generation signals and two-photon fluorescence lifetime datasets. The obtained data allowed us to differentiate healthy samples from tumor samples. These results confirmed the possible clinical relevance of this real-time multimodal optical analysis. This technique can be easily applied to neurosurgical procedures for a better delineation of surgical margins.

A new metric for detecting change in slowly evolving brain tumors: validation in meningioma patients.

PubMed

Pohl, Kilian M; Konukoglu, Ender; Novellas, Sebastian; Ayache, Nicholas; Fedorov, Andriy; Talos, Ion-Florin; Golby, Alexandra; Wells, William M; Kikinis, Ron; Black, Peter M

2011-03-01

Change detection is a critical component in the diagnosis and monitoring of many slowly evolving pathologies. This article describes a semiautomatic monitoring approach using longitudinal medical images. We test the method on brain scans of patients with meningioma, which experts have found difficult to monitor because the tumor evolution is very slow and may be obscured by artifacts related to image acquisition. We describe a semiautomatic procedure targeted toward identifying difficult-to-detect changes in brain tumor imaging. The tool combines input from a medical expert with state-of-the-art technology. The software is easy to calibrate and, in less than 5 minutes, returns the total volume of tumor change in mm. We test the method on postgadolinium, T1-weighted magnetic resonance images of 10 patients with meningioma and compare our results with experts' findings. We also perform benchmark testing with synthetic data. Our experiments indicated that experts' visual inspections are not sensitive enough to detect subtle growth. Measurements based on experts' manual segmentations were highly accurate but also labor intensive. The accuracy of our approach was comparable to the experts' results. However, our approach required far less user input and generated more consistent measurements. The sensitivity of experts' visual inspection is often too low to detect subtle growth of meningiomas from longitudinal scans. Measurements based on experts' segmentation are highly accurate but generally too labor intensive for standard clinical settings. We described an alternative metric that provides accurate and robust measurements of subtle tumor changes while requiring a minimal amount of user input.

Peritumoral Brain Edema after Stereotactic Radiosurgery for Asymptomatic Intracranial Meningiomas: Risks and Pattern of Evolution.

PubMed

Hoe, Yeon; Choi, Young Jae; Kim, Jeong Hoon; Kwon, Do Hoon; Kim, Chang Jin; Cho, Young Hyun

2015-10-01

To investigate the risks and pattern of evolution of peritumoral brain edema (PTE) after stereotactic radiosurgery (SRS) for asymptomatic intracranial meningiomas. A retrospective study was conducted on 320 patients (median age 56 years, range 24-87 years) who underwent primary Gamma Knife radiosurgery for asymptomatic meningiomas between 1998 and 2012. The median tumor volume was 2.7 cc (range 0.2-10.5 cc) and the median follow-up was 48 months (range 24-168 months). Volumetric data sets for tumors and PTE on serial MRIs were analyzed. The edema index (EI) was defined as the ratio of the volume of PTE including tumor to the tumor volume, and the relative edema indices (rEIs) were calculated from serial EIs normalized against the baseline EI. Risk factors for PTE were analyzed using logistic regression. Newly developed or increased PTE was noted in 49 patients (15.3%), among whom it was symptomatic in 28 patients (8.8%). Tumor volume larger than 4.2 cc (p<0.001), hemispheric tumor location (p=0.005), and pre-treatment PTE (p<0.001) were associated with an increased risk of PTE. rEI reached its maximum value at 11 months after SRS and decreased thereafter, and symptoms resolved within 24 months in most patients (85.7%). Caution should be exercised in decision-making on SRS for asymptomatic meningiomas of large volume (>4.2 cc), of hemispheric location, or with pre-treatment PTE. PTE usually develops within months, reaches its maximum degree until a year, and resolves within 2 years after SRS.

Evaluation of particle radiotherapy for the re-irradiation of recurrent intracranial meningioma.

PubMed

El Shafie, Rami A; Czech, Maja; Kessel, Kerstin A; Habermehl, Daniel; Weber, Dorothea; Rieken, Stefan; Bougatf, Nina; Jäkel, Oliver; Debus, Jürgen; Combs, Stephanie E

2018-05-08

With the advance of modern irradiation techniques, the role of radiotherapy (RT) for intracranial meningioma has increased significantly throughout the past years. Despite that tumor's generally favorable outcome with local control rates of up to 90% after ten years, progression after RT does occur. In those cases, re-irradiation is often difficult due to the limited radiation tolerance of the surrounding tissue. The aim of this analysis is to determine the value of particle therapy with its better dose conformity and higher biological efficacy for re-irradiating recurrent intracranial meningioma. It was performed within the framework of the "clinical research group heavy ion therapy" and funded by the German Research Council (DFG, KFO 214). Forty-two patients treated with particle RT (protons (n = 8) or carbon ions (n = 34)) for recurrent intracranial meningioma were included in this analysis. Location of the primary lesion varied, including skull base (n = 31), convexity (n = 5) and falx (n = 6). 74% of the patients were categorized high-risk according to histology with a WHO grading of II (n = 25) or III (n = 6), in the remaining cases histology was either WHO grade I (n = 10) or unknown (n = 1). Median follow-up was 49,7 months. In all patients, re-irradiation could be performed safely without interruptions due to side effects. No grade IV or V toxicities according to CTCAE v4.0 were observed. Particle RT offered good overall local control rates with 71% progression-free survival (PFS) after 12 months, 56,5% after 24 months and a median PFS of 34,3 months (95% CI 11,7-56,9). Histology had a significant impact on PFS yielding a median PFS of 25,7 months (95% CI 5,8-45,5) for high-risk histology (WHO grades II and III) while median PFS was not reached for low-risk tumors (WHO grade I) (p = 0,03). Median time to local progression was 15,3 months (Q1-Q3 8,08-34,6). Overall survival (OS) after re-irradiation was 89

Single-chain antibody-delivered Livin siRNA inhibits human malignant melanoma growth in vitro and in vivo.

PubMed

Wang, Hao; Yang, Yifei; Wang, Wei; Guan, Bing; Xun, Meng; Zhang, Hai; Wang, Ziling; Zhao, Yong

2017-05-01

Although gene therapy has brought new insights into the treatment of malignant melanoma, targeting delivery of nucleic acid which targets critical oncogene/anti-oncogene in vivo is still a bottleneck in the therapeutic application. Our previous in vitro studies have found that the oncogene Livin could serve as a potential molecular target by small interfering RNA for gene therapy of malignant melanoma. However, how to transport Livin small interfering RNA into malignant melanoma cells specifically and efficiently in vivo needs further investigation. Cumulative evidence has suggested that single-chain antibody-mediated small interfering RNA targeted delivery is an effective way to silence specific genes in human cancer cells. Indeed, this study designed a protamine-single-chain antibody fusion protein, anti-MM scFv-tP, to deliver Livin small interfering RNA into LiBr cells. Further experiments confirmed the induction of cell apoptosis and suppression of cell proliferation by anti-MM scFv-tP in LiBr cells, along with efficient silence of Livin gene both in vitro and in vivo. Altogether, our findings provide a feasible approach to transport Livin small interfering RNA to malignant melanoma cells which would be a new therapeutic strategy for combating malignant melanoma.

Diffusion Profiling via a Histogram Approach Distinguishes Low-grade from High-grade Meningiomas, Can Reflect the Respective Proliferative Potential and Progesterone Receptor Status.

PubMed

Gihr, Georg Alexander; Horvath-Rizea, Diana; Garnov, Nikita; Kohlhof-Meinecke, Patricia; Ganslandt, Oliver; Henkes, Hans; Meyer, Hans Jonas; Hoffmann, Karl-Titus; Surov, Alexey; Schob, Stefan

2018-02-01

Presurgical grading, estimation of growth kinetics, and other prognostic factors are becoming increasingly important for selecting the best therapeutic approach for meningioma patients. Diffusion-weighted imaging (DWI) provides microstructural information and reflects tumor biology. A novel DWI approach, histogram profiling of apparent diffusion coefficient (ADC) volumes, provides more distinct information than conventional DWI. Therefore, our study investigated whether ADC histogram profiling distinguishes low-grade from high-grade lesions and reflects Ki-67 expression and progesterone receptor status. Pretreatment ADC volumes of 37 meningioma patients (28 low-grade, 9 high-grade) were used for histogram profiling. WHO grade, Ki-67 expression, and progesterone receptor status were evaluated. Comparative and correlative statistics investigating the association between histogram profiling and neuropathology were performed. The entire ADC profile (p10, p25, p75, p90, mean, median) was significantly lower in high-grade versus low-grade meningiomas. The lower percentiles, mean, and modus showed significant correlations with Ki-67 expression. Skewness and entropy of the ADC volumes were significantly associated with progesterone receptor status and Ki-67 expression. ROC analysis revealed entropy to be the most accurate parameter distinguishing low-grade from high-grade meningiomas. ADC histogram profiling provides a distinct set of parameters, which help differentiate low-grade versus high-grade meningiomas. Also, histogram metrics correlate significantly with histological surrogates of the respective proliferative potential. More specifically, entropy revealed to be the most promising imaging biomarker for presurgical grading. Both, entropy and skewness were significantly associated with progesterone receptor status and Ki-67 expression and therefore should be investigated further as predictors for prognostically relevant tumor biological features. Since absolute ADC

Contemporary Endovascular Embolotherapy for Meningioma

PubMed Central

Dubel, Gregory J.; Ahn, Sun Ho; Soares, Gregory M.

2013-01-01

Preoperative endovascular tumor embolization has been used for 40 years. Meningiomas are the most common benign intracranial tumor in which preoperative embolization has been most extensively described in the literature. Advocates of embolization report that it reduces operative blood-loss, and softens the tumor, thus making surgery safer and easier. Opponents suggest that it adds additional risk and cost for patients without controlled studies showing conclusive benefit. The literature suggests a 3 to 6% neurological complication rate related to embolization. The combined external and internal carotid artery blood supply and complex anastomoses of the meninges can make embolization challenging. Positive outcomes require thorough knowledge of the pertinent vascular anatomy, familiarity with the neurovascular equipment and embolics, and meticulous technique. There remains debate on several aspects of embolization, including tumors most appropriate for embolization, embolic agent of choice, ideal size of embolic, and the choice of vessel(s) to embolize. This detailed review of pertinent vascular anatomy, embolization technique, results, and complications should allow practitioners to maximize treatment outcomes in this setting. PMID:24436548

The ESR1 and GPX1 gene expression level in human malignant and non-malignant breast tissues.

PubMed

Król, Magdalena B; Galicki, Michał; Grešner, Peter; Wieczorek, Edyta; Jabłońska, Ewa; Reszka, Edyta; Morawiec, Zbigniew; Wąsowicz, Wojciech; Gromadzińska, Jolanta

2018-01-01

The aim of this study was to establish whether the gene expression of estrogen receptor alpha (encoded by ESR1) correlates with the expression of glutathione peroxidase 1 (encoded by GPX1) in the tumor and adjacent tumor-free breast tissue, and whether this correlation is affected by breast cancer. Such relationships may give further insights into breast cancer pathology with respect to the status of estrogen receptor. We used the quantitative real-time PCR technique to analyze differences in the expression levels of the ESR1 and GPX1 genes in paired malignant and non-malignant tissues from breast cancer patients. ESR1 and GPX1 expression levels were found to be significantly down-regulated by 14.7% and 7.4% (respectively) in the tumorous breast tissue when compared to the non-malignant one. Down-regulation of these genes was independent of the tumor histopathology classification and clinicopathological factors, while the ESR1 mRNA level was reduced with increasing tumor grade (G1: 103% vs. G2: 85.8% vs. G3: 84.5%; p<0.05). In the non-malignant and malignant breast tissues, the expression levels of ESR1 and GPX1 were significantly correlated with each other (Rs=0.450 and Rs=0.360; respectively). Our data suggest that down-regulation of ESR1 and GPX1 was independent of clinicopathological factors. Down-regulation of ESR1 gene expression was enhanced by the development of the disease. Moreover, GPX1 and ESR1 gene expression was interdependent in the malignant breast tissue and further work is needed to determine the mechanism underlying this relationship.

Secreted primary human malignant mesothelioma exosome signature reflects oncogenic cargo

PubMed Central

Greening, David W.; Ji, Hong; Chen, Maoshan; Robinson, Bruce W. S.; Dick, Ian M.; Creaney, Jenette; Simpson, Richard J.

2016-01-01

Malignant mesothelioma (MM) is a highly-aggressive heterogeneous malignancy, typically diagnosed at advanced stage. An important area of mesothelioma biology and progression is understanding intercellular communication and the contribution of the secretome. Exosomes are secreted extracellular vesicles shown to shuttle cellular cargo and direct intercellular communication in the tumour microenvironment, facilitate immunoregulation and metastasis. In this study, quantitative proteomics was used to investigate MM-derived exosomes from distinct human models and identify select cargo protein networks associated with angiogenesis, metastasis, and immunoregulation. Utilising bioinformatics pathway/network analyses, and correlation with previous studies on tumour exosomes, we defined a select mesothelioma exosomal signature (mEXOS, 570 proteins) enriched in tumour antigens and various cancer-specific signalling (HPGD/ENO1/OSMR) and secreted modulators (FN1/ITLN1/MAMDC2/PDGFD/GBP1). Notably, such circulating cargo offers unique insights into mesothelioma progression and tumour microenvironment reprogramming. Functionally, we demonstrate that oncogenic exosomes facilitate the migratory capacity of fibroblast/endothelial cells, supporting the systematic model of MM progression associated with vascular remodelling and angiogenesis. We provide biophysical and proteomic characterisation of exosomes, define a unique oncogenic signature (mEXOS), and demonstrate the regulatory capacity of exosomes in cell migration/tube formation assays. These findings contribute to understanding tumour-stromal crosstalk in the context of MM, and potential new diagnostic and therapeutic extracellular targets. PMID:27605433

Micro-RNAs as diagnostic or prognostic markers in human epithelial malignancies

PubMed Central

2011-01-01

Micro-RNAs (miRs) are important regulators of mRNA and protein expression; the ability of miR expression profilings to distinguish different cancer types and classify their sub-types has been well-described. They also represent a novel biological entity with potential value as tumour biomarkers, which can improve diagnosis, prognosis, and monitoring of treatment response for human cancers. This endeavour has been greatly facilitated by the stability of miRs in formalin-fixed paraffin-embedded (FFPE) tissues, and their detection in circulation. This review will summarize some of the key dysregulated miRs described to date in human epithelial malignancies, and their potential value as molecular bio-markers in FFPE tissues and blood samples. There remain many challenges in this domain, however, with the evolution of different platforms, the complexities of normalizing miR profiling data, and the importance of evaluating sufficiently-powered training and validation cohorts. Nonetheless, well-conducted miR profiling studies should contribute important insights into the molecular aberrations driving human cancer development and progression. PMID:22128797

Bevacizumab in Reducing CNS Side Effects in Patients Who Have Undergone Radiation Therapy to the Brain for Primary Brain Tumor, Meningioma, or Head and Neck Cancer

ClinicalTrials.gov

2014-04-21

Adult Anaplastic Astrocytoma; Adult Anaplastic Ependymoma; Adult Anaplastic Meningioma; Adult Anaplastic Oligodendroglioma; Adult Brain Stem Glioma; Adult Central Nervous System Germ Cell Tumor; Adult Choroid Plexus Tumor; Adult Diffuse Astrocytoma; Adult Ependymoma; Adult Grade II Meningioma; Adult Grade III Meningioma; Adult Malignant Hemangiopericytoma; Adult Mixed Glioma; Adult Oligodendroglioma; Adult Papillary Meningioma; Adult Pineocytoma; Malignant Neoplasm; Meningeal Melanocytoma; Radiation Toxicity; Recurrent Adenoid Cystic Carcinoma of the Oral Cavity; Recurrent Adult Brain Tumor; Recurrent Basal Cell Carcinoma of the Lip; Recurrent Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity; Recurrent Inverted Papilloma of the Paranasal Sinus and Nasal Cavity; Recurrent Lymphoepithelioma of the Nasopharynx; Recurrent Lymphoepithelioma of the Oropharynx; Recurrent Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity; Recurrent Mucoepidermoid Carcinoma of the Oral Cavity; Recurrent Salivary Gland Cancer; Recurrent Squamous Cell Carcinoma of the Hypopharynx; Recurrent Squamous Cell Carcinoma of the Larynx; Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity; Recurrent Squamous Cell Carcinoma of the Nasopharynx; Recurrent Squamous Cell Carcinoma of the Oropharynx; Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Recurrent Verrucous Carcinoma of the Larynx; Recurrent Verrucous Carcinoma of the Oral Cavity; Stage I Adenoid Cystic Carcinoma of the Oral Cavity; Stage I Basal Cell Carcinoma of the Lip; Stage I Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity; Stage I Inverted Papilloma of the Paranasal Sinus and Nasal Cavity; Stage I Lymphoepithelioma of the Nasopharynx; Stage I Lymphoepithelioma of the Oropharynx; Stage I Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity; Stage I Mucoepidermoid Carcinoma of the Oral Cavity; Stage I Salivary Gland Cancer; Stage I Squamous Cell Carcinoma

Tunneling Nanotubes Provide a Unique Conduit for Intercellular Transfer of Cellular Contents in Human Malignant Pleural Mesothelioma

PubMed Central

Lou, Emil; Fujisawa, Sho; Morozov, Alexei; Barlas, Afsar; Romin, Yevgeniy; Dogan, Yildirim; Gholami, Sepideh; Moreira, André L.; Manova-Todorova, Katia; Moore, Malcolm A. S.

2012-01-01

Tunneling nanotubes are long, non-adherent F-actin-based cytoplasmic extensions which connect proximal or distant cells and facilitate intercellular transfer. The identification of nanotubes has been limited to cell lines, and their role in cancer remains unclear. We detected tunneling nanotubes in mesothelioma cell lines and primary human mesothelioma cells. Using a low serum, hyperglycemic, acidic growth medium, we stimulated nanotube formation and bidirectional transfer of vesicles, proteins, and mitochondria between cells. Notably, nanotubes developed between malignant cells or between normal mesothelial cells, but not between malignant and normal cells. Immunofluorescent staining revealed their actin-based assembly and structure. Metformin and an mTor inhibitor, Everolimus, effectively suppressed nanotube formation. Confocal microscopy with 3-dimensional reconstructions of sectioned surgical specimens demonstrated for the first time the presence of nanotubes in human mesothelioma and lung adenocarcinoma tumor specimens. We provide the first evidence of tunneling nanotubes in human primary tumors and cancer cells and propose that these structures play an important role in cancer cell pathogenesis and invasion. PMID:22427958

Refractory seizures due to a dural-based cavernoma masquerading as a meningioma.

PubMed

Zeng, Xianwei; Mahta, Ali; Kim, Ryan Y; Saad, Ali G; Kesari, Santosh

2012-04-01

A 37-year-old female presented with medically intractable complex partial seizures with secondary generalization. She was found to have a dural-based lesion with radiologic features of meningioma. A gross total resection was performed and pathology confirmed a diagnosis of cavernous angioma and she became seizure free after the surgical resection. Cavernous angioma should be considered in differential diagnosis of a dural-based lesion manifesting with refractory seizures.

Mechanical deterioration underlies malignant behavior of aneurysmal human ascending aorta.

PubMed

Koullias, George; Modak, Raj; Tranquilli, Maryann; Korkolis, Dimitris P; Barash, Paul; Elefteriades, John A

2005-09-01

The human ascending aorta becomes markedly prone to rupture and dissection at a diameter of 6 cm. The mechanical substrate for this malignant behavior is unknown. This investigation applied engineering analysis to human ascending aortic aneurysms and compared their structural characteristics with those of normal aortas. We measured the mechanical characteristics of the aorta by direct epiaortic echocardiography at the time of surgery in 33 patients with ascending aortic aneurysm undergoing aortic replacement and in 20 control patients with normal aortas undergoing coronary artery bypass grafting. Six parameters were measured in all patients: aortic diameter in systole and diastole, aortic wall thickness in systole and diastole, and blood pressure in systole and diastole. These were used to calculate mechanical characteristics of the aorta from standard equations. Aortic distensibility reflects the elastic qualities of the aorta. Aortic wall stress reflects the disrupting force experienced within the aortic wall. Incremental elastic modulus indicates loss of elasticity reserve. Aortic distensibility falls to extremely low levels as aortic dimension rises toward 6 cm (3.02 mm Hg(-1) for small aortas versus 1.45 mm Hg(-1) for aortas larger than 5 cm, P < .05). Aortic wall stress rises to 157.8 kPa for the aneurysmal aorta, compared with 92.5 kPa for normal aortas. For 6-cm aortas at pressures of 200 mm Hg or more, wall stress rises to 857 kPa, nearly exceeding the known maximal tensile strength of human aneurysmal aortic wall. Incremental elastic modulus deteriorates (1.93 +/- 0.88 MPa vs 1.18 +/- 0.21 MPa, P < .05) in aneurysmal aortas relative to that in normal aortas. The mechanical properties of the aneurysmal aorta deteriorate dramatically as the aorta enlarges, reaching critical levels associated with rupture by a diameter of 6 cm. This mechanical deterioration provides an explanation in engineering terms for the malignant clinical behavior (rupture and

Novel BAFF-Receptor Antibody to Natively Folded Recombinant Protein Eliminates Drug-Resistant Human B-cell Malignancies In Vivo.

PubMed

Qin, Hong; Wei, Guowei; Sakamaki, Ippei; Dong, Zhenyuan; Cheng, Wesley A; Smith, D Lynne; Wen, Feng; Sun, Han; Kim, Kunhwa; Cha, Soungchul; Bover, Laura; Neelapu, Sattva S; Kwak, Larry W

2018-03-01

Purpose: mAbs such as anti-CD20 rituximab are proven therapies in B-cell malignancies, yet many patients develop resistance. Novel therapies against alternative targets are needed to circumvent resistance mechanisms. We sought to generate mAbs against human B-cell-activating factor receptor (BAFF-R/TNFRSF13C), which has not yet been targeted successfully for cancer therapy. Experimental Design: Novel mAbs were generated against BAFF-R, expressed as a natively folded cell surface immunogen on mouse fibroblast cells. Chimeric BAFF-R mAbs were developed and assessed for in vitro and in vivo monotherapy cytotoxicity. The chimeric mAbs were tested against human B-cell tumor lines, primary patient samples, and drug-resistant tumors. Results: Chimeric antibodies bound with high affinity to multiple human malignant B-cell lines and induced potent antibody-dependent cellular cytotoxicity (ADCC) against multiple subtypes of human lymphoma and leukemia, including primary tumors from patients who had relapsed after anti-CD20 therapy. Chimeric antibodies also induced ADCC against ibrutinib-resistant and rituximab-insensitive CD20-deficient variant lymphomas, respectively. Importantly, they demonstrated remarkable in vivo growth inhibition of drug-resistant tumor models in immunodeficient mice. Conclusions: Our method generated novel anti-BAFF-R antibody therapeutics with remarkable single-agent antitumor effects. We propose that these antibodies represent an effective new strategy for targeting and treating drug-resistant B-cell malignancies and warrant further development. Clin Cancer Res; 24(5); 1114-23. ©2017 AACR . ©2017 American Association for Cancer Research.

Human brain cancer studied by resonance Raman spectroscopy

NASA Astrophysics Data System (ADS)

Zhou, Yan; Liu, Cheng-Hui; Sun, Yi; Pu, Yang; Boydston-White, Susie; Liu, Yulong; Alfano, Robert R.

2012-11-01

The resonance Raman (RR) spectra of six types of human brain tissues are examined using a confocal micro-Raman system with 532-nm excitation in vitro. Forty-three RR spectra from seven subjects are investigated. The spectral peaks from malignant meningioma, stage III (cancer), benign meningioma (benign), normal meningeal tissues (normal), glioblastoma multiforme grade IV (cancer), acoustic neuroma (benign), and pituitary adenoma (benign) are analyzed. Using a 532-nm excitation, the resonance-enhanced peak at 1548 cm-1 (amide II) is observed in all of the tissue specimens, but is not observed in the spectra collected using the nonresonance Raman system. An increase in the intensity ratio of 1587 to 1605 cm-1 is observed in the RR spectra collected from meningeal cancer tissue as compared with the spectra collected from the benign and normal meningeal tissue. The peak around 1732 cm-1 attributed to fatty acids (lipids) are diminished in the spectra collected from the meningeal cancer tumors as compared with the spectra from normal and benign tissues. The characteristic band of spectral peaks observed between 2800 and 3100 cm-1 are attributed to the vibrations of methyl (-CH3) and methylene (-CH2-) groups. The ratio of the intensities of the spectral peaks of 2935 to 2880 cm-1 from the meningeal cancer tissues is found to be lower in comparison with that of the spectral peaks from normal, and benign tissues, which may be used as a distinct marker for distinguishing cancerous tissues from normal meningeal tissues. The statistical methods of principal component analysis and the support vector machine are used to analyze the RR spectral data collected from meningeal tissues, yielding a diagnostic sensitivity of 90.9% and specificity of 100% when two principal components are used.

Tratamiento Quirúrgico de los Meningiomas del Foramen Óptico, Técnicay Resultados de una Serie de 18 Pacientes

PubMed Central

Goldschmidt, Ezequiel; Ajler, Pablo; Campero, Álvaro; Landriel, Federico; Sposito, Maximiliano; Carrizo, Antonio

2014-01-01

Introducción: los meningiomas del foramen óptico producen un rápido deterioro de la función visual aún cuando su tamaño es pequeño, por eso su diagnóstico y manejo difiere del resto de los meningiomas clinoideos. El propósito de este estudio es presentar la técnica y los resultados de nuestro manejo quirúrgico de meningiomas foraminales (MF). Pacientes y Métodos: se llevó a cabo una revisión de las historias clínicas de 47 pacientes con meningiomas primarios intraorbitarios. Se realizaron 52 cirugías en los pacientes con MF. Se empleó una craneotomía fronto-orbitaria, seguida de una descompresión extradural del canal óptico, resección del componente intraorbitario y exploración intradural del nervio óptico. Resultados: de los 12 pacientes con MF que presentaban la visión conservada, la agudeza visual fue preservada en 7 casos, mejoró en 2, y empeoró en 3. En 18 pacientes, el principal síntoma fue exoftalmos y en 35 pacientes ceguera unilateral. Ocurrieron 6 recurrencias, 2 a 10 años después de la resección quirúrgica. Cinco de ellos fueron reoperados. Se indicó radioterapia después de la recurrencia en 3 pacientes. Conclusión: el manejo de los MF continúa siendo controvertido y frecuentemente se propone un tratamiento conservador. Basados en nuestros hallazgos de frecuente extensión intracraneal, proponemos realizar una resección total o subtotal del tumor, preservando el nervio óptico en pacientes con visión prequirúrgica conservada. PMID:25165616

Type 2 diabetes is an independent negative prognostic factor in patients undergoing surgical resection of a WHO grade I meningioma.

PubMed

Nayeri, Arash; Chotai, Silky; Prablek, Marc A; Brinson, Philip R; Douleh, Diana G; Weaver, Kyle D; Thompson, Reid C; Chambless, Lola

2016-10-01

In recent years, there has been increased recognition of the relationship between type 2 diabetes mellitus (DM) and poor outcomes following a variety of surgical procedures. We sought to study the role of type 2 DM as a prognostic factor affecting the long-term survival of patients undergoing surgical resection of a WHO Grade I meningioma. We conducted a retrospective cohort study on 196 patients who had a WHO Grade I meningioma resected at our institution between 2001 and 2013. The medical record was reviewed to identify a pre-existing diagnosis of type 2 DM. Patient mortality was reviewed by medical record and Social Security Death Index (SSDI). Variables associated with survival in a univariate analysis were included in the multivariate Cox model if P<0.10. Variables with probability values >0.05 were then removed from the multivariate model in a step-wise fashion. 33 (17%) patients had pre-existing diagnoses of type 2 DM prior to clinical presentation. Mean survival time in diabetic patients was 52.1 months compared to 160.9 months in non-diabetics. The decreased survival rate and time in patients with type 2 DM were found to be statistically significant (p=0.008 and p<0.0001, respectively). In a multivariate Cox analysis, a pre-existing history of type 2 DM was independently associated with decreased survival following the resection of a WHO Grade I meningioma (HR=2.6, p=0.045). A pre-existing diagnosis of type 2 DM is an independent negative prognostic indicator following the resection of a WHO Grade I meningioma. Copyright © 2016 Elsevier B.V. All rights reserved.

Comparisons among MRI signs, apparent diffusion coefficient, and fractional anisotropy in dogs with a solitary intracranial meningioma or histiocytic sarcoma.

PubMed

Wada, Masae; Hasegawa, Daisuke; Hamamoto, Yuji; Yu, Yoshihiko; Fujiwara-Igarashi, Aki; Fujita, Michio

2017-07-01

Although MRI has become widely used in small animal practice, little is known about the validity of advanced MRI techniques such as diffusion-weighted imaging and diffusion tensor imaging. The aim of this retrospective analytical observational study was to investigate the characteristics of diffusion parameters, that is the apparent diffusion coefficient and fractional anisotropy, in dogs with a solitary intracranial meningioma or histiocytic sarcoma. Dogs were included based on the performance of diffusion MRI and histological confirmation. Statistical analyses were performed to compare apparent diffusion coefficient and fractional anisotropy for the two types of tumor in the intra- and peritumoral regions. Eleven cases with meningioma and six with histiocytic sarcoma satisfied the inclusion criteria. Significant differences in apparent diffusion coefficient value (× 10 -3 mm 2 /s) between meningioma vs. histiocytic sarcoma were recognized in intratumoral small (1.07 vs. 0.76) and large (1.04 vs. 0.77) regions of interest, in the peritumoral margin (0.93 vs. 1.08), and in the T2 high region (1.21 vs. 1.41). Significant differences in fractional anisotropy values were found in the peritumoral margin (0.29 vs. 0.24) and the T2 high region (0.24 vs. 0.17). The current study identified differences in measurements of apparent diffusion coefficient and fractional anisotropy for meningioma and histiocytic sarcoma in a small sample of dogs. In addition, we observed that all cases of intracranial histiocytic sarcoma showed leptomeningeal enhancement and/or mass formation invading into the sulci in the contrast study. Future studies are needed to determine the sensitivity of these imaging characteristics for differentiating between these tumor types. © 2017 American College of Veterinary Radiology.

Effect of human cell malignancy on activity of DNA polymerase iota.

PubMed

Kazakov, A A; Grishina, E E; Tarantul, V Z; Gening, L V

2010-07-01

An increased level of mutagenesis, partially caused by imbalanced activities of error prone DNA polymerases, is a key symptom of cell malignancy. To clarify the possible role of incorrect DNA polymerase iota (Pol iota) function in increased frequency of mutations in mammalian cells, the activity of this enzyme in extracts of cells of different mouse organs and human eye (melanoma) and eyelid (basal-cell skin carcinoma) tumor cells was studied. Both Mg2+, considered as the main activator of the enzyme reaction of in vivo DNA replication, and Mn2+, that activates homogeneous Pol iota preparations in experiments in vitro more efficiently compared to all other bivalent cations, were used as cofactors of the DNA polymerase reaction in these experiments. In the presence of Mg2+, the enzyme was active only in cell extracts of mouse testicles and brain, whereas in the presence of Mn2+ the activity of Pol iota was found in all studied normal mouse organs. It was found that in cell extracts of both types of malignant tumors (basal-cell carcinoma and melanoma) Pol iota activity was observed in the presence of either Mn2+ or Mg2+. Manganese ions activated Pol iota in both cases, though to a different extent. In the presence of Mn2+ the Pol iota activity in the basal-cell carcinoma exceeded 2.5-fold that in control cells (benign tumors from the same eyelid region). In extracts of melanoma cells in the presence of either cation, the level of the enzyme activity was approximately equal to that in extracts of cells of surrounding tumor-free tissues as well as in eyes removed after traumas. The distinctive feature of tissue malignancy (in basal-cell carcinoma and in melanoma) was the change in DNA synthesis revealed as Mn2+-activated continuation of DNA synthesis after incorrect incorporation of dG opposite dT in the template by Pol iota. Among cell extracts of different normal mouse organs, only those of testicles exhibited a similar feature. This similarity can be explained by

Trigeminal complications arising after surgery of cranial base meningiomas.

PubMed

Westerlund, Ulf; Linderoth, Bengt; Mathiesen, Tiit

2012-04-01

Chronic severe facial pain is a feared sequel of cranial base surgery. This study explores the symptomatology, incidence and impact on the individual of postoperative de novo trigeminal nerve affection as well as the recovery potential. Out of 231 patients operated for cranial base meningiomas at the Karolinska University Hospital during 7 years, 25 complained of de novo trigeminal symptoms at clinical follow-up 3 months after surgery. Six were later lost to follow-up leaving 19 participants in the study, which was conducted using a questionnaire and a structured telephone interview. All patients complained of facial numbness, affecting the V1 branch in 10/19 patients (53%), the V2 branch in 18/19 (95%) and the V3 branch in 9/19 (47%). Surprisingly, only three (16%) suffered from trigeminal pain, which could be adequately managed by pharmacotherapy. However, five patients (26%) demonstrated ocular dysaesthetic problems. Twelve (63%) described their handicap to be mild, while seven (37%) had daily or severe symptoms. Five patients (26%) reported no improvement over time, while nine (47%) showed improvement and four (21%) stated good recovery. Only one patient (5%) claimed complete symptom remission. In the present study, 11% of the patients presented with a de novo postoperative affection of the trigeminal nerve after removal of a cranial base meningioma; 37% of these reported daily/severe symptoms. Only 26% showed good recovery, observed in patients without tumour infiltration of the nerve or intraoperative nerve damage. In spite of frequent complaints of numbness, pain was uncommon (16%) and often manageable by pharmacotherapy, while ocular symptoms turned out to be more frequent and more disabling than expected.

Somatostatin Receptor SPECT/CT using 99mTc Labeled HYNIC-TOC Aids in Diagnosis of Primary Optic Nerve Sheath Meningioma.

PubMed

Chandra, Piyush; Purandare, Nilendu; Shah, Sneha; Agrawal, Archi; Rangarajan, Venkatesh

2017-01-01

Primary optic nerve sheath meningiomas (ONSM) are rare, benign and slow growing tumor involving the intra-orbital/intra-canalicular segment of the optic nerve. Untreated, they can potentially lead to visual deterioration. Magnetic resonance (MR) is the gold standard imaging modality for diagnosing the entity. Often, a clinical dilemma exists to narrow the differential diagnosis of an enhancing intra-orbital mass on MR. Molecular imaging provides a high degree of precision in diagnosing meningioma in view of relatively high levels of somatostatin receptor expression by these tumors. The following case demonstrates the potential clinical utility of somatostatin receptor SPECT using 99m Tc- labeled HYNIC-TOC in clinical diagnosis of ONSM.

Surgery in elderly patients with intracranial meningioma: neuropsychological functioning during a long term follow-up.

PubMed

Di Cristofori, Andrea; Zarino, Barbara; Bertani, Giulio; Locatelli, Marco; Rampini, Paolo; Carrabba, Giorgio; Caroli, Manuela

2018-05-01

Surgical treatment of elderly patients with meningioma is has proved to be safe, especially when patients are selected using dedicated surgical scores. These scores take into account tumor size, edema, location and patient's co-morbidities. Neuropsychological functioning (NPF) of this kind of patients has been poorly studied in literature and it is not taken into account by these scores. Aim of our study was to describe the long-term outcome in terms of NPF of elderly patients undergoing surgery. Patients older than 70 years of age affected by intracranial meningioma and selected with the Clinical-Radiological Grading Score were included in our study. Neuropsychological testing was performed using a dedicated battery of tests before surgery, 3 and 12 months after surgery. Clinical, neurological and radiological outcomes were studied as well. Forty-one patients with a median age of 74 years were included in this study. Preoperatively only 1/41 patients showed a normal NPF with all tests scoring normally. Four out of 39 patients showed a complete neuropsychological recovery after 3 months; while 10/37 patients had a complete recovery after 12 months. NPF showed a trend of progressive improvement after surgery. Our study is the first experience reported in literature describing a long term follow-up in elderly patients after surgery for intracranial meningioma. In our series, surgery determined an improvement of NPF over time; especially with a low complication rate related to the selection of patients obtained through the CRGS. Further studies need to be performed in order to understand how brain edema, tumor size, volume and tumor location affect NPF in both short and long term.

Meningiomas involving the optic nerve: technical aspects and outcomes for a series of 50 patients.

PubMed

Margalit, Nevo S; Lesser, Jonathan B; Moche, Jason; Sen, Chandranath

2003-09-01

Surgical strategies and results for 50 patients with meningiomas involving the optic nerves are discussed and evaluated. Factors affecting the degree of resection and patient outcomes are presented. We emphasize our surgical techniques for resection of these tumors and we discuss the advantages of different approaches, depending on the relationship of the tumor to the optic nerves. Data for 50 patients with meningiomas involving the optic nerves who were surgically treated between 1991 and 2002 were reviewed, by using patient files, operative notes, and pre- and postoperative imaging and ophthalmological examination findings. Thirty-one female patients and 19 male patients, with a mean age of 53 years, were treated. Thirty-one patients (62%) underwent complete tumor removal (Simpson Grade 1 or 2), and 19 patients underwent subtotal removal (Grade 4). Factors affecting the grade of resection were tumor size (P = 0.01), location (P = 0.007), and internal carotid artery encasement (P = 0.019). Patients who underwent Grade 1 or 2 resection exhibited a mean tumor size of 3.0 cm, and patients who underwent Grade 4 resection exhibited a mean tumor size of 4.1 cm. Only three patients had residual tumor on the optic nerve; all others had tumor in the cavernous sinus or at the orbital apex or exhibited vascular involvement. Visual outcomes were influenced predominantly by tumor size, preoperative visual function, and optic nerve encasement. Meningiomas that involve the optic nerves require special considerations and surgical techniques. Early decompression of the optic nerve within the bony canal allows identification and separation of the tumor from the nerve, permitting removal of the tumor from this area with minimal manipulation of the optic nerve.

Endoscopic Endonasal and Transcranial Surgery for Microsurgical Resection of Ventral Foramen Magnum Meningiomas: A Preliminary Experience.

PubMed

Khattar, Nicolas; Koutourousiou, Maria; Chabot, Joseph D; Wang, Eric W; Cohen-Gadol, Aaron A; Snyderman, Carl H; Fernandez-Miranda, Juan C; Gardner, Paul A

2018-05-01

Purely ventral foramen magnum meningiomas are challenging tumors to treat given their location, and proximity and relationship to vital neurovascular structures. To present endoscopic endonasal surgery (EES) as a complementary approach to the far-lateral suboccipital approach (FLA) for ventral midline tumors. From May 2008 to October 2013, 5 patients underwent EES and 5 FLA for primary ventral foramen magnum meningiomas. We retrospectively reviewed their records to evaluate outcomes. Nine of 10 patients presented with long-tract and lower cranial nerve deficits. All patients who presented with deficits preoperatively completely normalized after tumor resection regardless of approach. Gross total resection was achieved in 2 cases in the EES group and 4 cases in the FLA group (the rest were near total). Vascular encasement was a limitation to gross total resection with both approaches. Preoperative median Karnofsky Performance Scale score was 80 and improved to 100 in both groups. Following EES, 1 patient developed cerebrospinal fluid leak with resultant meningitis. Two patients developed hydrocephalus, one of which developed an epidural abscess following necrosis of the nasoseptal flap, requiring debridement. In the FLA group, 1 patient developed a pseudomeningocele associated with hydrocephalus. One patient developed an abdominal fat graft site hematoma. Both approaches provide excellent results for resection of ventral foramen magnum meningiomas, with reconstruction and hydrocephalus as the main sources of complication. In our practice, EES is a preferred technique in ventral, purely midline tumors with limited inferior extension and reduced lower cranial nerve manipulation, whereas FLA is preferred in tumors with lateral and caudal extension below the tip of the dens.

Image-guided sphenoid wing meningioma resection and simultaneous computer-assisted cranio-orbital reconstruction: technical case report.

PubMed

Westendorff, Carsten; Kaminsky, Jan; Ernemann, Ulrike; Reinert, Siegmar; Hoffmann, Jürgen

2007-02-01

Resection of large intraosseous sphenoid wing meningiomas is traditionally associated with significant morbidity. Rapid prototyping techniques have become widely used for treatment planning. Yet, the transfer of a treatment plan into the intraoperative situs strongly depends on the experience of the individual surgeon. Extensive resection with orbital decompression was planned and performed on the basis of rapid prototyping and surgical navigation techniques in a 44-year-old woman presenting with a large sphenoid wing meningioma on the right infiltrating the orbit. Tumor resection was simulated on a stereolithography model of the patient's head. The stereolithography model was scanned using computed tomography (CT) and the defect geometry was used to create a custom-made titanium implant. The implant consisted of a solid titanium core and a spot-welded titanium mesh surrounding the core, allowing for minor intraoperative adjustments of the implant size by reducing the mesh size. The stereolithography model with the incorporated implant was CT scanned again and the CT data were fused with the patient's original CT data. The implant borders indicating the resection borders were marked within the patient's CT data set. This treatment plan was transferred to an optical navigation system. Intraoperatively, tumor resection was performed using surgical navigation. In the presented case report, the combination of computer-assisted planning using rapid prototyping techniques and image-guided surgery allowed for an extensive tumor resection precisely according to a preoperative treatment plan in a patient presenting with a large intraosseous sphenoid wing meningioma. A larger clinical series with a long-term follow-up period will be needed to determine the reproducibility.

Large sphenocavernous meningiomas: is there still a role for the intradural approach via the pterional-transsylvian route?

PubMed

Tomasello, F; de Divitiis, O; Angileri, F F; Salpietro, F M; d'Avella, D

2003-04-01

Large-sized sphenocavernous meningiomas represent a surgical challenge. Although the role of skull base techniques with combined extra- and intradural steps has been recently emphasized, pure intradural resection tactics via the pterional route constitute the traditional microsurgical approach for resection of such tumours. We report the application of the pterional-transsylvian approach in 13 patients with sphenocavernous meningiomas. This series is unique because it includes only patients with tumours exceeding 5 cm in their greatest dimension. A gross total resection was accomplished in 10 patients (77%). Eight patients had a good outcome, one had a persistent mild hemiparesis, and one died. No recurrences occurred in this group. Three patients (23%) had subtotal resections owing to invasion of the cavernous sinus in one instance and encasement of the middle cerebral artery in the others. Two had a good outcome and one died. In these patients minimal asymptomatic tumour progression was seen 3 and 6 years after surgery. The overall surgical outcome was good in 10 patients (77%), fair in one, and death in two. In our experience, large sphenocavernous meningiomas may be operated on adopting pure intradural resection tactics via the pterional-transsylvian route with rates of gross total removal and surgical complications related to brain retraction or vascular manipulation comparable to those of extensive skull base approaches. The traditional intradural pterional transsylvian approach continues to have a place in the treatment of these lesions.

The Origin of Malignant Malaria

USDA-ARS?s Scientific Manuscript database

Plasmodium falciparum is the causative agent of malignant malaria, which is among the most severe human infectious diseases. Despite its overwhelming significance to human health, the parasite’s origins remain unclear. The favored origin hypothesis holds that P. falciparum and its closest known rel...

Systemic distribution, subcellular localization and differential expression of sphingosine-1-phosphate receptors in benign and malignant human tissues

PubMed Central

Wang, Chunyi; Mao, Jinghe; Redfield, Samantha; Mo, Yinyuan; Lage, Janice M.; Zhou, Xinchun

2014-01-01

Aims Five sphingosine-1-phosphate receptors (S1PR): S1PR1, S1PR2, S1PR3, S1PR4 and S1PR5 (S1PR1-5) have been shown to be involved in the proliferation and progression of various cancers. However, none of the S1PRs have been systemically investigated. In this study, we performed immunohistochemistry (IHC) for S1PR1-S1PR5 on different tissues, in order to simultaneously determine the systemic distribution, subcellular localization and expression level of all five S1PRs. Methods We constructed tissue microarrays (TMAs) from 384 formalin-fixed paraffin-embedded (FFPE) blocks containing 183 benign and 201 malignant tissues from 34 human organs/systems. Then we performed IHC for all five S1PRs simultaneously on these TMA slides. The distribution, subcellular localization and expression of each S1PR were determined for each tissue. The data were then compared in benign and malignant tissues from the same organ/tissue using the student t-test. In order to reconfirm the subcellular localization of each S1PR as determined by IHC, immunocytochemistry (ICC) was performed on several malignant cell lines. Results We found that all five S1PRs are widely distributed in multiple human organs/systems. All S1PRs are expressed in both the cytoplasm and nucleus, except S1PR3, whose IHC signals are only seen in the nucleus. Interestingly, the S1PRs are rarely expressed on cellular membranes. Each S1PR is unique in its organ distribution, subcellular localization and expression level in benign and malignant tissues. Among the five S1PRs, S1PR5 has the highest expression level (either in nucleus or cytoplasm), with S1PR1, 3, 2 and 4 following in descending order. Strong nuclear expression was seen for S1PR1, S1PR3 and S1PR5, whereas S1PR2 and S1PR4 show only weak staining. Four organs/tissues (adrenal gland, liver, brain and colon) show significant differences in IHC scores for the multiple S1PRs (nuclear and/or cytoplasmic), nine (stomach, lymphoid tissues, lung, ovary, cervix, pancreas

Following the canyon to reach and remove olfactory groove meningiomas.

PubMed

Stefini, Roberto; Zenga, Francesco; Giacomo, Esposito; Bolzoni, Andrea; Tartara, Fulvio; Spena, Giannantonio; Ambrosi, Claudia; Fontanella, Marco M

2017-04-01

Olfactory groove meningiomas (OGMs) represent approximately 10% of all intracranial meningiomas. They arise in the olfactory fossa, a variable depression delimited by the lateral lamella and perpendicular plate. The cribriform plate with the lateral lamella and ethmoidal and orbital roof could be viewed as a 'canyon' with the frontal sinus as the main entrance. Between January 2000 and December 2013, 32 consecutive patients underwent removal of OGMs through this 'canyon' at the Department of Neurosurgery of Brescia and Turin. Complete removal was achieved in all patients with this trans-frontal sinus subcranial approach (Simpson grade I; mean lesion volume, 46.6 cm3). Five patients (15.6%) experienced nasal CSF leakage, treated with external lumbar drain positioning for 4 days and resolved in all cases but one, which was re-operated. Two patients (6.2%) during the CSF leakage experienced meningitis at day 7 after surgery, both successfully treated by intravenous antibiotic therapy. After one month, one patient developed hydrocephalus, treated with a ventricular peritoneal shunt. In one patient, traction on the OGM caused bleeding of the callosomarginal artery, which was coagulated with superior frontal gyrus ischemia without neurological consequences. Glasgow Outcome Scale Score at 6 months was V in 29 patients, IV in one patient, and I in two patients. Advantages with this approach may include easy and early control of blood supply from its insertion in the skull base, minimal frontal lobe retraction, preservation of the frontal veins draining to the sagittal sinus, and a satisfactory aesthetic outcome.

Clinical outcome after high-precision radiotherapy for skull base meningiomas: Pooled data from three large German centers for radiation oncology.

PubMed

Combs, Stephanie E; Farzin, Mostafa; Boehmer, Julia; Oehlke, Oliver; Molls, Michael; Debus, Jürgen; Grosu, Anca-Ligia

2018-05-01

To evaluate outcome in patients with base of skull meningiomas treated with modern high precision radiation therapy (RT) techniques. 927 patients from three centers were treated with either radiosurgery or fractionated high-precision RT for meningiomas. Treatment planning was based on CT and MRI following institutional guidelines. For radiosurgery, a median dose of 13 Gy was applied, for fractionated treatments, a median dose of 54 Gy in 1.8 Gy single fractions was prescribed. Follow-up included a clinical examination as well as contrast-enhanced imaging. All patients were followed up prospectively after radiotherapy in the three departments within a strict follow-up regimen. The median follow-up time was 81 months (range 1-348 months). Median local control was 79 months (range 1-348 months). Local control (LC) was 98% at 1 year, 94% at 3 years, 92% at 5 years and 86% at 10 years. There was no difference between radiosurgery and fractionated RT. We analyzed the influence of higher doses on LC and could show that dose did not impact LC. Moreover, there was no difference between 54 Gy and 57.6 Gy in the fractionated group. Side effects were below 5% in both groups without any severe treatment-related complications. Based on the pooled data analysis this manuscript provides a large series of meningiomas of the skull base treated with modern high precision RT demonstrating excellent local control and low rates of side effects. Such data support the recommendation of RT for skull base meningiomas in the interdisciplinary tumor board discussions. The strong role of RT must influence treatment recommendations keeping in mind the individual risk-benefit profile of treatment alternatives. Copyright © 2018 Elsevier B.V. All rights reserved.

Gamma knife surgery-induced ependymoma after the treatment of meningioma - a case report.

PubMed

Wang, Ke; Pan, Li; Che, Xiaoming; Lou, Meiqing

2012-01-01

Gamma knife surgery is widely used for a number of neurological disorders. However, little is known about its long-term complications such as carcinogenic risks. Here, we present a case of a radiosurgery-induced ependymoma by gamma knife surgery for the treatment of a spinal meningioma in a 7-year-old patient. In light of reviewing the previous reports, we advocate high caution in making young patients receive this treatment.

Hemostasis and malignancy.

PubMed

Francis, J L; Biggerstaff, J; Amirkhosravi, A

1998-01-01

There is considerable evidence that the hemostatic system is involved in the growth and spread of malignant disease. There is an increased incidence of thromboembolic disease in patients with cancers and hemostatic abnormalities are extremely common in such patients. Antihemostatic agents have been successfully used to treat a variety of experimental tumors, and several clinical trials in humans have been initiated. Although metastasis is undoubtedly multifactorial, intravascular coagulation activation and peritumor fibrin deposition seem to be important. The mechanisms by which hemostatic activation facilitates the malignant process remain to be completely elucidated. Of central importance may be the presence on malignant cells of tissue factor and urokinase receptor. Recent studies have suggested that these proteins, and others, may be involved at several stages of metastasis, including the key event of neovascularization. Tissue factor, the principal initiator of coagulation, may have additional roles, outside of fibrin formation, that are central to the biology of some solid tumors.

Olfactory groove meningiomas from neurosurgical and ear, nose, and throat perspectives: approaches, techniques, and outcomes.

PubMed

Spektor, Sergey; Valarezo, Javier; Fliss, Dan M; Gil, Ziv; Cohen, Jose; Goldman, Jose; Umansky, Felix

2005-10-01

To review the surgical approaches, techniques, outcomes, and recurrence rates in a series of 80 olfactory groove meningioma (OGM) patients operated on between 1990 and 2003. Eighty patients underwent 81 OGM surgeries. Tumor diameter varied from 2 to 9 cm (average, 4.6 cm). In 35 surgeries (43.2%), the tumor was removed through bifrontal craniotomy; nine operations (11.1%) were performed through a unilateral subfrontal approach; 18 surgeries (22.2%) were performed through a pterional approach; seven surgeries (8.6%) were carried out using a fronto-orbital craniotomy; and 12 procedures (14.8%) were accomplished via a subcranial approach. Nine patients (11.3%) had undergone surgery previously and had recurrent tumor. Total removal was obtained in 72 patients (90.0%); subtotal removal was achieved in 8 patients (10.0%). Two patients, one with total and one with subtotal removal, had atypical (World Health Organization Grade II) meningiomas, whereas 78 patients had World Health Organization Grade I tumors. There was no operative mortality and no new permanent focal neurological deficit besides anosmia. Twenty-five patients (31.3%) experienced surgery-related complications. There were no recurrences in 75 patients (93.8%) 6 to 164 months (mean, 70.8 mo) after surgery. Three patients (3.8%) were lost to follow-up. In two patients (2.5%) with subtotal removal, the residual evidenced growth on computed tomography and/or magnetic resonance imaging 1 year after surgery. One of them had an atypical meningioma. The second, a multiple meningiomata patient, was operated on twice in this series. A variety of surgical approaches are used for OGM resection. An approach tailored to the tumor's size, location, and extension, combined with modern microsurgical cranial base techniques, allows full OGM removal with minimal permanent morbidity, excellent neurological outcome, and very low recurrence rates.

Turner syndrome and meningioma: support for a possible increased risk of neoplasia in Turner syndrome.

PubMed

Pier, Danielle B; Nunes, Fabio P; Plotkin, Scott R; Stemmer-Rachamimov, Anat O; Kim, James C; Shih, Helen A; Brastianos, Priscilla; Lin, Angela E

2014-01-01

Neoplasia is uncommon in Turner syndrome, although there is some evidence that brain tumors are more common in Turner syndrome patients than in the general population. We describe a woman with Turner syndrome (45,X) with a meningioma, in whom a second neoplasia, basal cell carcinomas of the scalp and nose, developed five years later in the absence of therapeutic radiation. Together with 7 cases of Turner syndrome with meningioma from a population-based survey in the United Kingdom, and 3 other isolated cases in the literature, we review this small number of patients for evidence of risk factors related to Turner syndrome, such as associated structural anomalies or prior treatment. We performed histological and fluorescent in situ hybridization (FISH) of 22q (NF2 locus) analyses of the meningeal tumor to search for possible molecular determinants. We are not able to prove causation between these two entities, but suggest that neoplasia may be a rare associated medical problem in Turner syndrome. Additional case reports and extension of population-based studies are needed. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Fluorescence Behavior and Dural Infiltration of Meningioma Analyzed by 5-Aminolevulinic Acid-Based Fluorescence: Operating Microscope Versus Mini-Spectrometer.

PubMed

Knipps, Johannes; Beseoglu, Kerim; Kamp, Marcel; Fischer, Igor; Felsberg, Joerg; Neumann, Lisa M; Steiger, Hans-Jakob; Cornelius, Jan F

2017-12-01

To compare fluorescence intensity of tumor specimens, as measured by a fluorescence-guided surgery microscope and a spectrometer, to evaluate tumor infiltration of dura mater around meningiomas with help of these 2 different 5-aminolevulinic acid (5-ALA)-based fluorescence tools, and to correlate fluorescence intensity with histopathologic data. In a clinical series, meningiomas were resected by 5-ALA fluorescence-guided surgery. Fluorescence intensity was semiquantitatively rated by the surgeon at predefined points. Biopsies were harvested and fluorescence intensity measured by a spectrometer and histopathologically analyzed. Sampling was realized at the level of the dura in a centrifugal direction. A total of 104 biopsies (n = 13 tumors) were analyzed. Specificity and sensitivity of the microscope were 0.96 and 0.53 and of the spectrometer 0.95 and 0.93, respectively. Fluorescence intensity as measured by the spectrometer was correlated to histologically confirmed tumor burden. In a centrifugal direction, tumor burden and fluorescence intensity continuously decreased (along the dural tail). Below a threshold value of 639 arbitrary units no tumor was histologically detectable. At the level of the dura the spectrometer was highly sensitive for detection of meningioma cells. The surgical microscope showed false negative results and missed residual tumor cells in more than one half of the cases. The complementary use of both fluorescence tools may improve resection quality. Copyright © 2017 Elsevier Inc. All rights reserved.

Influence of surgery and dexamethasone on cell-mediated immune responses in patients with meningiomas.

PubMed Central

Pees, H. W.

1977-01-01

Cell-mediated cytotoxicity (CTX) was studied in meningioma patients before and within 2 weeks of complete excision of the tumour, using the [3H]-prolin- microcytotoxicity test. Three of 7 patients tested before surgery showed specific CTX, 2 revealed a "non-specific" (tumour-unrelated) response, and 2 were non-reactive. After surgery, CTX decreased from 84 to 50% in one patient and became negative in 2 others previously positive. One of 2 patients showing "non-specific" CTX preoperatively became positive, while the other remained unchanged. All patients were receiving dexamethasone (DXM) at the time they were tested. Lymphocyte responses to PHA were not significantly different before or after surgery (i.e. after prolonged treatment with DXM), from healthy controls. Blocking activity could be detected in the sera of all 3 patients before surgery. This activity was not specific for meningiomas. Paradoxically, the same sera did not inhibit the proliferative response to PHA. Serum from only one patient consistently suppressed the blastogenic response of homologous lymphocytes to PHA. Inhibitory activity was associated with the IgG fraction of his serum. Images Fig. 1 PMID:861144

Use of 5-aminolevulinic acid in fluorescence-guided resection of meningioma with high risk of recurrence. Case report.

PubMed

Kajimoto, Yoshinaga; Kuroiwa, Toshihiko; Miyatake, Shin-Ichi; Ichioka, Tsugumichi; Miyashita, Minoru; Tanaka, Hidekazu; Tsuji, Motomu

2007-06-01

It has been established that fluorescence-guided resection using 5-aminolevulinic acid (5-ALA) is useful in glioma surgery. The authors report on a 65-year-old woman who had a huge atypical left-hemisphere meningioma, which extended into the skull and to the superior sagittal sinus and demonstrated fluorescence in response to administration of 5-ALA. After the tumor was removed, the operative field was observed under the fluorescent mode of a fluorescence surgical microscopy system. Several minute areas of residual tumor tissue were visualized as strong fluorescence behind the vein and sinus, in a part of the hypertrophic dura, and along the edge of the skull. These remnants were completely removed. The authors concluded that fluorescence-guided resection using 5-ALA is useful in cases of atypical meningiomas with a high risk of recurrence.

Systemic distribution, subcellular localization and differential expression of sphingosine-1-phosphate receptors in benign and malignant human tissues.

PubMed

Wang, Chunyi; Mao, Jinghe; Redfield, Samantha; Mo, Yinyuan; Lage, Janice M; Zhou, Xinchun

2014-10-01

Five sphingosine-1-phosphate receptors (S1PR): S1PR1, S1PR2, S1PR3, S1PR4 and S1PR5 (S1PR1-5) have been shown to be involved in the proliferation and progression of various cancers. However, none of the S1PRs have been systemically investigated. In this study, we performed immunohistochemistry (IHC) for S1PR1-S1PR5 on different tissues, in order to simultaneously determine the systemic distribution, subcellular localization and expression level of all five S1PRs. We constructed tissue microarrays (TMAs) from 384 formalin-fixed paraffin-embedded (FFPE) blocks containing 183 benign and 201 malignant tissues from 34 human organs/systems. Then we performed IHC for all five S1PRs simultaneously on these TMA slides. The distribution, subcellular localization and expression of each S1PR were determined for each tissue. The data in benign and malignant tissues from the same organ/tissue were then compared using the Student's t-test. In order to reconfirm the subcellular localization of each S1PR as determined by IHC, immunocytochemistry (ICC) was performed on several malignant cell lines. We found that all five S1PRs are widely distributed in multiple human organs/systems. All S1PRs are expressed in both the cytoplasm and nucleus, except S1PR3, whose IHC signals are only seen in the nucleus. Interestingly, the S1PRs are rarely expressed on cellular membranes. Each S1PR is unique in its organ distribution, subcellular localization and expression level in benign and malignant tissues. Among the five S1PRs, S1PR5 has the highest expression level (in either the nucleus or cytoplasm), with S1PR1, 3, 2 and 4 following in descending order. Strong nuclear expression was seen for S1PR1, S1PR3 and S1PR5, whereas S1PR2 and S1PR4 show only weak staining. Four organs/tissues (adrenal gland, liver, brain and colon) show significant differences in IHC scores for the multiple S1PRs (nuclear and/or cytoplasmic), nine (stomach, lymphoid tissues, lung, ovary, cervix, pancreas, skin, soft

Planum Sphenoidale and Tuberculum Sellae Meningiomas: Operative Nuances of a Modern Surgical Technique with Outcome and Proposal of a New Classification System.

PubMed

Mortazavi, Martin M; Brito da Silva, Harley; Ferreira, Manuel; Barber, Jason K; Pridgeon, James S; Sekhar, Laligam N

2016-02-01

The resection of planum sphenoidale and tuberculum sellae meningiomas is challenging. A universally accepted classification system predicting surgical risk and outcome is still lacking. We report a modern surgical technique specific for planum sphenoidale and tuberculum sellae meningiomas with associated outcome. A new classification system that can guide the surgical approach and may predict surgical risk is proposed. We conducted a retrospective review of the patients who between 2005 and March 2015 underwent a craniotomy or endoscopic surgery for the resection of meningiomas involving the suprasellar region. Operative nuances of a modified frontotemporal craniotomy and orbital osteotomy technique for meningioma removal and reconstruction are described. Twenty-seven patients were found to have tumors arising mainly from the planum sphenoidale or the tuberculum sellae; 25 underwent frontotemporal craniotomy and tumor removal with orbital osteotomy and bilateral optic canal decompression, and 2 patients underwent endonasal transphenoidal resection. The most common presenting symptom was visual disturbance (77%). Vision improved in 90% of those who presented with visual decline, and there was no permanent visual deterioration. Cerebrospinal fluid leak occurred in one of the 25 cranial cases (4%) and in 1 of 2 transphenoidal cases (50%), and in both cases it resolved with treatment. There was no surgical mortality. An orbitotomy and early decompression of the involved optic canal are important for achieving gross total resection, maximizing visual improvement, and avoiding recurrence. The visual outcomes were excellent. A new classification system that can allow the comparison of different series and approaches and indicate cases that are more suitable for an endoscopic transsphenoidal approach is presented. Copyright © 2016 Elsevier Inc. All rights reserved.

Different expression of FoxM1 in human benign and malignant pleural effusion.

PubMed

Tang, Zhonghao; Li, Hongqing; Zhu, Huili; Bai, Chunxue

2015-01-01

The aims of this study were as follows: to analyze the forkhead box M1 (FoxM1) expression in benign and malignant pleural effusion by reverse transcription-polymerase chain reaction assay (RT-PCR); to explore the role of FoxM1 in formation and progress in malignant pleural effusion, and whether there is significant difference in expression level of FoxM1 between benign and malignant pleural effusion; to seek a gene marker diagnostically useful to identify benign and malignant pleural effusion in diagnosis and treatment of pleural effusion; and to collect expression level data of FoxM1 in 23 malignant pleural effusion samples (17 adenocarcinoma samples, four squamous carcinoma samples and two small cell lung carcinoma samples) and 15 benign pleural effusion samples (11 inflammatory pleural effusions, two transudates, two tuberculous pleural effusions) by RT-PCR. Among all 38 samples, average FoxM1 expression level of benign pleural effusions is (235.09 ± 59.99), while malignant pleural effusions (828.77 ± 109.76). Among 23 malignant samples, average FoxM1 expression level is (529.27 ± 75.85) in samples without cytological diagnostic evidence, while (1,218.12 ± 167.21) in samples with cytological diagnostic evidence. Differences of FoxM1 expression level between benign pleural effusions and malignant ones have statistical significance. There is an area of 0.881 under the receiver-operating characteristic curve, which verifies the accuracy of using FoxM1 expression level as diagnostic index to identify benign and malignant pleural effusions. According to our study, diagnostic sensitivity and specificity for FoxM1 expression level at 418.1 were 82.6 and 86.7 %, respectively, while 47.8 and 100 %, respectively, at 768.7. FoxM1 expression level in malignant pleural effusions is significantly higher than in benign ones. This study provides a new approach in clinical diagnosis, with FoxM1 as a specific molecule marker to identify benign and malignant pleural

PTEN: Multiple Functions in Human Malignant Tumors.

PubMed

Milella, Michele; Falcone, Italia; Conciatori, Fabiana; Cesta Incani, Ursula; Del Curatolo, Anais; Inzerilli, Nicola; Nuzzo, Carmen M A; Vaccaro, Vanja; Vari, Sabrina; Cognetti, Francesco; Ciuffreda, Ludovica

2015-01-01

PTEN is the most important negative regulator of the PI3K signaling pathway. In addition to its canonical, PI3K inhibition-dependent functions, PTEN can also function as a tumor suppressor in a PI3K-independent manner. Indeed, the PTEN network regulates a broad spectrum of biological functions, modulating the flow of information from membrane-bound growth factor receptors to nuclear transcription factors, occurring in concert with other tumor suppressors and oncogenic signaling pathways. PTEN acts through its lipid and protein phosphatase activity and other non-enzymatic mechanisms. Studies conducted over the past 10 years have expanded our understanding of the biological role of PTEN, showing that in addition to its ability to regulate proliferation and cell survival, it also plays an intriguing role in regulating genomic stability, cell migration, stem cell self-renewal, and tumor microenvironment. Changes in PTEN protein levels, location, and enzymatic activity through various molecular mechanisms can generate a continuum of functional PTEN levels in inherited syndromes, sporadic cancers, and other diseases. PTEN activity can indeed, be modulated by mutations, epigenetic silencing, transcriptional repression, aberrant protein localization, and post-translational modifications. This review will discuss our current understanding of the biological role of PTEN, how PTEN expression and activity are regulated, and the consequences of PTEN dysregulation in human malignant tumors.

PTEN: Multiple Functions in Human Malignant Tumors

PubMed Central

Milella, Michele; Falcone, Italia; Conciatori, Fabiana; Cesta Incani, Ursula; Del Curatolo, Anais; Inzerilli, Nicola; Nuzzo, Carmen M. A.; Vaccaro, Vanja; Vari, Sabrina; Cognetti, Francesco; Ciuffreda, Ludovica

2015-01-01

PTEN is the most important negative regulator of the PI3K signaling pathway. In addition to its canonical, PI3K inhibition-dependent functions, PTEN can also function as a tumor suppressor in a PI3K-independent manner. Indeed, the PTEN network regulates a broad spectrum of biological functions, modulating the flow of information from membrane-bound growth factor receptors to nuclear transcription factors, occurring in concert with other tumor suppressors and oncogenic signaling pathways. PTEN acts through its lipid and protein phosphatase activity and other non-enzymatic mechanisms. Studies conducted over the past 10 years have expanded our understanding of the biological role of PTEN, showing that in addition to its ability to regulate proliferation and cell survival, it also plays an intriguing role in regulating genomic stability, cell migration, stem cell self-renewal, and tumor microenvironment. Changes in PTEN protein levels, location, and enzymatic activity through various molecular mechanisms can generate a continuum of functional PTEN levels in inherited syndromes, sporadic cancers, and other diseases. PTEN activity can indeed, be modulated by mutations, epigenetic silencing, transcriptional repression, aberrant protein localization, and post-translational modifications. This review will discuss our current understanding of the biological role of PTEN, how PTEN expression and activity are regulated, and the consequences of PTEN dysregulation in human malignant tumors. PMID:25763354

Olfactory groove meningioma: discussion of clinical presentation and surgical outcomes following excision via the subcranial approach.

PubMed

Pepper, Jon-Paul; Hecht, Sarah L; Gebarski, Stephen S; Lin, Erin M; Sullivan, Stephen E; Marentette, Lawrence J

2011-11-01

To describe surgical outcomes and radiographic features of olfactory groove meningiomas treated by excision through the subcranial approach. Special emphasis is placed on paranasal sinus and orbit involvement. Retrospective review of a series of patients. Nineteen patients underwent excision of olfactory groove meningioma (OGM) via the transglabellar/subcranial approach between December 1995 and November 2009. Nine patients had previously undergone prior resection at outside institutions, and four had prior radiotherapy in addition to a prior excision. Transglabellar/subcranial surgical approach to the anterior skull base was performed. Tumor histology included three World Health Organization (WHO) grade III lesions, one WHO grade II lesion, and 15 WHO grade I lesions. Fourteen patients had evidence of extension into the paranasal sinuses, with the ethmoid sinus being most commonly involved. Kaplan-Meier estimates of mean overall and disease-free survival were 121.45 months and 93.03 months, respectively. The mean follow-up interval was 41.0 months, and at the time of data analysis three patients had recurrent tumors. Seven (36.8%) patients experienced a major complication in the perioperative period; there were no perioperative mortalities. Orbit invasion was observed in four patients, with optic nerve impingement in 11 patients. Of these, three patients had long-term diplopia. No patients experienced worsening of preoperative visual acuity. Olfactory groove meningiomas demonstrate a propensity to spread into the paranasal sinuses, particularly in recurrent cases. Given a tendency for infiltrative recurrence along the skull base, this disease represents an important area of collaboration between neurosurgery and otolaryngology. The subcranial approach offers excellent surgical access for excision, particularly for recurrences that involve the paranasal sinuses and optic apparatus. Copyright © 2011 The American Laryngological, Rhinological, and Otological Society

Transcription analysis in the MeLiM swine model identifies RACK1 as a potential marker of malignancy for human melanocytic proliferation.

PubMed

Egidy, Giorgia; Julé, Sophia; Bossé, Philippe; Bernex, Florence; Geffrotin, Claudine; Vincent-Naulleau, Silvia; Horak, Vratislav; Sastre-Garau, Xavier; Panthier, Jean-Jacques

2008-04-28

Metastatic melanoma is a severe disease. Few experimental animal models of metastatic melanoma exist. MeLiM minipigs exhibit spontaneous melanoma. Cutaneous and metastatic lesions are histologically similar to human's. However, most of them eventually spontaneously regress. Our purpose was to investigate whether the MeLiM model could reveal markers of malignancy in human melanocytic proliferations. We compared the serial analysis of gene expression (SAGE) between normal pig skin melanocytes and melanoma cells from an early pulmonary metastasis of MeLiM minipigs. Tag identification revealed 55 regulated genes, including GNB2L1 which was found upregulated in the melanoma library. In situ hybridisation confirmed GNB2L1 overexpression in MeLiM melanocytic lesions. GNB2L1 encodes the adaptor protein RACK1, recently shown to influence melanoma cell lines tumorigenicity. We studied the expression of RACK1 by immunofluorescence and confocal microscopy in tissues specimens of normal skin, in cutaneous and metastatic melanoma developped in MeLiM minipigs and in human patients. In pig and human samples, the results were similar. RACK1 protein was not detected in normal epidermal melanocytes. By contrast, RACK1 signal was highly increased in the cytoplasm of all melanocytic cells of superficial spreading melanoma, recurrent dermal lesions and metastatic melanoma. RACK1 partially colocalised with activated PKCalphabeta. In pig metastases, additional nuclear RACK1 did not associate to BDNF expression. In human nevi, the RACK1 signal was low. RACK1 overexpression detected in situ in human melanoma specimens characterized cutaneous and metastatic melanoma raising the possibility that RACK1 can be a potential marker of malignancy in human melanoma. The MeLiM strain provides a relevant model for exploring mechanisms of melanocytic malignant transformation in humans. This study may contribute to a better understanding of melanoma pathophysiology and to progress in diagnosis.

[Management of cerebellopontine angle meningiomas and the posterior part of the temporal bone. Report on 44 cases].

PubMed

Le Garlantezec, C; Vidal, V Franco; Guerin, J; Bébéar, J P; Liguoro, D; Darrouzet, V

2005-01-01

To review and study the management of CPA meningiomas through the experience of an otoneurosurgical team. Fourty-two patients (44 meningiomas) were considered. Seventy-seven per cent of tumors (34 cases) were operated on; 6 tumors (14.6%) were exclusively irradiated using fractionated radiation therapy (FRT) and four only surveyed (9,8%). transpetrosal approaches were exclusively used. These were translabyrinthine (TLA) in 47%, widened retrolabyrinthine (WRLA) in 41% of cases, transcochlear approach (TCA) in three cases and a middle fossa in one. A transtentorial approach was combined in 35% of cases (8 TLA, 4 WRLA). Surgical removal was incomplete in 11,8% of cases; in 3 cases growing tumor was treated by FRT included one case of anaplasic tumor Postoperative complications were: 1 meningitis, 1 wound abscess, 2 hydrocephalus (6%) and 4 CSF fistulas (12%). No complications have been observed during the last 7 years (21 cases). House and Brackmann Grade 1 or 2 facial function was obtained in 59% of cases (but 10 patients had a preoperative facial nerve paresis). A normal or subnormal AAO-HNS Class A-B Hearing could be preserved in 57% of WRLA. Radiation therapy allowed tumor shrinkage in all cases. In 3 cases this regression was of more than 50%. Surgery is the gold standard in treating CPA meningiomas. Transpetrosal approaches and particularly WRLA pure or combined to a transtentorial approach are for us the best way to remove these tumors in preserving hearing and facial nerve function. When hearing is poor or when tumor extension to the clivus or the premeatal area is consistent a TLA is either planned preoperatively or obtained from a WRLA.

Effect of tranexamic acid on intraoperative blood loss and transfusion requirements in patients undergoing excision of intracranial meningioma.

PubMed

Hooda, Bhavna; Chouhan, Rajendra Singh; Rath, Girija Prasad; Bithal, Parmod Kumar; Suri, Ashish; Lamsal, Ritesh

2017-07-01

Surgical excision of meningioma is often complicated by significant blood loss requiring blood transfusion with its attendant risks. Although tranexamic acid is used to reduce perioperative blood loss, its blood conservation effect is uncertain in neurosurgery. Sixty adults undergoing elective craniotomy for meningioma excision were randomized to receive either tranexamic acid or placebo, initiated prior to skin incision. Patients in the tranexamic acid group received intravenous bolus of 20mg/kg over 20min followed by an infusion of 1mg/kg/h till the conclusion of surgery. Intraoperative blood loss, transfusion requirements and estimation of surgical hemostasis using a 5-grade scale were noted. Postoperatively, the extent of tumor excision on CT scan and complications were observed. Demographics, tumor characteristics, amount of fluid infusion, and duration of surgery and anesthesia were comparable between the two groups. The amount of blood loss was significantly less in tranexamic acid group compared to placebo (830mlvs 1124ml; p=0.03). The transfusion requirement was less in tranexamic acid group (p>0.05). The patients in tranexamic acid group fared better on a 5-grade surgical hemostasis scale with more patients showing good hemostasis (p=0.007). There were no significant differences between the groups with regards to extent of tumor removal, perioperative complications, hospital stay or neurologic outcome. To conclude, administration of tranexamic acid significantly reduced blood loss in patients undergoing excision of meningioma. Fewer patients in the tranexamic acid group received blood transfusions. Surgical field hemostasis was better achieved in patients who received tranexamic acid. Copyright © 2017 Elsevier Ltd. All rights reserved.

A less invasive surgical concept for the resection of spinal meningiomas.

PubMed

Boström, A; Bürgel, U; Reinacher, P; Krings, T; Rohde, V; Gilsbach, J M; Hans, F J

2008-06-01

The surgical strategy for spinal meningiomas usually consists of laminectomy, initial tumour debulking, identification of the interface between tumour and spinal cord, resection of the dura including the matrix of the tumour, and duroplasty. The objective of this study was to investigate whether a less invasive surgical strategy consisting of hemilaminectomy or laminectomy, tumour removal and coagulation of the tumour matrix allows comparable surgical and clinical results to be obtained, especially without an increase of the recurrence rate as reported in the literature. Between 1990 and 2005, 61 patients (11 men, 50 women) underwent surgery for spinal meningioma. All patients were treated microsurgically by a posterior approach. In 56 of the 61 patients, the above outlined - less invasive - surgical technique with tumour removal and coagulation of the tumour matrix was performed. In 5 patients, dura resection and duroplasty was additionally performed. Electrophysiological monitoring was routinely used since 1996. Recurrence was defined as new onset or worsening of symptoms and radiological confirmation of tumour growth. The pre-and post-operative clinical status was measured by the Frankel grading system. Pre-operatively, 40 patients were in Frankel grade D, 13 patients in grade C, 6 patients in grade E and 1 patient each in grade A and B. Following surgery no patient presented a permanent worsening of clinical symptoms. All patients who initially presented with a Frankel grades A-C (n = 15) recovered to a better grade at the time of follow-up. Patients who presented with Frankel grade D remained in stable condition (n = 27) or recovered to a better neurological status (n = 13). Two patients experienced a temporary worsening of their symptoms, but subsequently improved to a better state than pre-operatively. Two (3.3%) complications (pseudomeningocele, wound infection) requiring surgery, were encountered. The pseudomeningocele developed in a patient who underwent

The incidence of postoperative thromboembolic complications following surgical resection of intracranial meningioma. A retrospective study of a large single center patient cohort.

PubMed

Hoefnagel, Daphna; Kwee, Lesley E; van Putten, Erik H P; Kros, Johan M; Dirven, Clemens M F; Dammers, Ruben

2014-08-01

Patients with meningiomas carry an increased risk for postoperative venous thromboembolic complications (VTE) including deep venous thrombosis (DVT) and pulmonary embolism (PE). In the present retrospective study we investigated the incidence of VTE and the risk factors involved, in a large cohort of patients surgically treated for an intracranial meningioma at our institution. During the period from January 1997 to January 2009, 581 consecutive patients underwent craniotomy for intracranial meningioma. All patients received low-molecular weight heparins as thromboembolism prophylaxis. Patient demographics and tumor characteristics were gathered via retrospective chart review. Postoperative VTE and hemorrhages were noted. Backward stepwise logistic regression was used to determine the risk factors. 80.6% of meningiomas were WHO grade 1; 15.1% WHO grade 2; 4.3% WHO grade 3. Postoperative VTE were observed in 41 patients (7.2%). Of these, DVT was seen in 20 (3.5%) and PE in 26 patients (4.6%). The thromboembolic complication appeared on average 21.1±29.2 days post surgery. The 90-day mortality rate after VTE was 11.2% (23.1% for PE and 5.0% for DVT). Postoperative hemorrhages requiring surgical treatment were found in 2.9% of patients. Risk factors for VTE were body mass index (p=0.015) for DVT; weight (p=0.001) and bedridden postoperatively (p=0.001) for PE; and weight (p=0.004) and bedridden postoperatively (p=0.003) for VTE in general. There was no relation between tumor grade and thromboembolic complications. The major risk factors for postoperative VTE found in our single center study are patient weight and a bedridden status postoperatively. Prophylactic intervention for this potentially fatal complication should be evaluated against the relative lower risk of postoperative hemorrhages. Copyright © 2014 Elsevier B.V. All rights reserved.

Development of a new high-affinity human antibody with antitumor activity against solid and blood malignancies.

PubMed

Sioud, Mouldy; Westby, Phuong; Vasovic, Vlada; Fløisand, Yngvar; Peng, Qian

2018-04-16

mAbs have emerged as a promising strategy for the treatment of cancer. However, in several malignancies, no effective antitumor mAbs are yet available. Identifying therapeutic mAbs that recognize common tumor antigens could render the treatment widely applicable. Here, a human single-chain variable fragment (scFv) antibody library was sequentially affinity selected against a panel of human cancer cell lines and an antibody fragment (named MS5) that bound to solid and blood cancer cells was identified. The MS5 scFv was fused to the human IgG1 Fc domain to generate an antibody (MS5-Fc fusion) that induced antibody-dependent cellular cytotoxicity and phagocytosis of cancer cells by macrophages. In addition, the MS5-Fc antibody bound to primary leukemia cells and induced antibody-dependent cellular cytotoxicity. In the majority of analyzed cancer cells, the MS5-Fc antibody induced cell surface redistribution of the receptor complexes, but not internalization, thus maximizing the accessibility of the IgG1 Fc domain to immune effector cells. In vitro stability studies showed that the MS5-Fc antibody was stable after 6 d of incubation in human serum, retaining ∼60% of its initial intact form. After intravenous injections, the antibody localized into tumor tissues and inhibited the growth of 3 different human tumor xenografts (breast, lymphoma, and leukemia). These antitumor effects were associated with tumor infiltration by macrophages and NK cells. In the Ramos B-cell lymphoma xenograft model, the MS5-Fc antibody exhibited a comparable antitumor effect as rituximab, a chimeric anti-CD20 IgG1 mAb. These results indicate that human antibodies with pan-cancer abilities can be generated from phage display libraries, and that the engineered MS5-Fc antibody could be an attractive agent for further clinical investigation.-Sioud, M., Westby, P., Vasovic, V., Fløisand, Y., Peng, Q. Development of a new high-affinity human antibody with antitumor activity against solid and

FOXM1 upregulation is an early event in human squamous cell carcinoma and it is enhanced by nicotine during malignant transformation.

PubMed

Gemenetzidis, Emilios; Bose, Amrita; Riaz, Adeel M; Chaplin, Tracy; Young, Bryan D; Ali, Muhammad; Sugden, David; Thurlow, Johanna K; Cheong, Sok-Ching; Teo, Soo-Hwang; Wan, Hong; Waseem, Ahmad; Parkinson, Eric K; Fortune, Farida; Teh, Muy-Teck

2009-01-01

Cancer associated with smoking and drinking remains a serious health problem worldwide. The survival of patients is very poor due to the lack of effective early biomarkers. FOXM1 overexpression is linked to the majority of human cancers but its mechanism remains unclear in head and neck squamous cell carcinoma (HNSCC). FOXM1 mRNA and protein expressions were investigated in four independent cohorts (total 75 patients) consisting of normal, premalignant and HNSCC tissues and cells using quantitative PCR (qPCR), expression microarray, immunohistochemistry and immunocytochemistry. Effect of putative oral carcinogens on FOXM1 transcriptional activity was dose-dependently assayed and confirmed using a FOXM1-specific luciferase reporter system, qPCR, immunoblotting and short-hairpin RNA interference. Genome-wide single nucleotide polymorphism (SNP) array was used to 'trace' the genomic instability signature pattern in 8 clonal lines of FOXM1-induced malignant human oral keratinocytes. Furthermore, acute FOXM1 upregulation in primary oral keratinocytes directly induced genomic instability. We have shown for the first time that overexpression of FOXM1 precedes HNSCC malignancy. Screening putative carcinogens in human oral keratinocytes surprisingly showed that nicotine, which is not perceived to be a human carcinogen, directly induced FOXM1 mRNA, protein stabilisation and transcriptional activity at concentrations relevant to tobacco chewers. Importantly, nicotine also augmented FOXM1-induced transformation of human oral keratinocytes. A centrosomal protein CEP55 and a DNA helicase/putative stem cell marker HELLS, both located within a consensus loci (10q23), were found to be novel targets of FOXM1 and their expression correlated tightly with HNSCC progression. This study cautions the potential co-carcinogenic effect of nicotine in tobacco replacement therapies. We hypothesise that aberrant upregulation of FOXM1 may be inducing genomic instability through a program of

FOXM1 Upregulation Is an Early Event in Human Squamous Cell Carcinoma and it Is Enhanced by Nicotine during Malignant Transformation

PubMed Central

Gemenetzidis, Emilios; Bose, Amrita; Riaz, Adeel M.; Chaplin, Tracy; Young, Bryan D.; Ali, Muhammad; Sugden, David; Thurlow, Johanna K.; Cheong, Sok-Ching; Teo, Soo-Hwang; Wan, Hong; Waseem, Ahmad; Parkinson, Eric K.; Fortune, Farida; Teh, Muy-Teck

2009-01-01

Background Cancer associated with smoking and drinking remains a serious health problem worldwide. The survival of patients is very poor due to the lack of effective early biomarkers. FOXM1 overexpression is linked to the majority of human cancers but its mechanism remains unclear in head and neck squamous cell carcinoma (HNSCC). Methodology/Principal Findings FOXM1 mRNA and protein expressions were investigated in four independent cohorts (total 75 patients) consisting of normal, premalignant and HNSCC tissues and cells using quantitative PCR (qPCR), expression microarray, immunohistochemistry and immunocytochemistry. Effect of putative oral carcinogens on FOXM1 transcriptional activity was dose-dependently assayed and confirmed using a FOXM1-specific luciferase reporter system, qPCR, immunoblotting and short-hairpin RNA interference. Genome-wide single nucleotide polymorphism (SNP) array was used to ‘trace’ the genomic instability signature pattern in 8 clonal lines of FOXM1-induced malignant human oral keratinocytes. Furthermore, acute FOXM1 upregulation in primary oral keratinocytes directly induced genomic instability. We have shown for the first time that overexpression of FOXM1 precedes HNSCC malignancy. Screening putative carcinogens in human oral keratinocytes surprisingly showed that nicotine, which is not perceived to be a human carcinogen, directly induced FOXM1 mRNA, protein stabilisation and transcriptional activity at concentrations relevant to tobacco chewers. Importantly, nicotine also augmented FOXM1-induced transformation of human oral keratinocytes. A centrosomal protein CEP55 and a DNA helicase/putative stem cell marker HELLS, both located within a consensus loci (10q23), were found to be novel targets of FOXM1 and their expression correlated tightly with HNSCC progression. Conclusions/Significance This study cautions the potential co-carcinogenic effect of nicotine in tobacco replacement therapies. We hypothesise that aberrant upregulation

Endoscopic transnasal resection of anterior cranial fossa meningiomas.

PubMed

de Divitiis, Enrico; Esposito, Felice; Cappabianca, Paolo; Cavallo, Luigi M; de Divitiis, Oreste; Esposito, Isabella

2008-01-01

The extended transnasal approach, a recent surgical advancements for the ventral skull base, allows excellent midline access to and visibility of the anterior cranial fossa, which was previously thought to be approachable only via a transcranial route. The extended transnasal approach allows early decompression of the optic canals, obviates the need for brain retraction, and reduces neurovascular manipulation. Between 2004 and 2007, 11 consecutive patients underwent transnasal resection of anterior cranial fossa meningiomas--4 olfactory groove (OGM) and 7 tuberculum sellae (TSM) meningiomas. Age at surgery, sex, symptoms, and imaging studies were reviewed. Tumor size and tumor extension were estimated, and the anteroposterior, vertical, and horizontal diameters were measred on MR images. Medical records, surgical complications, and outcomes of the patients were collected. A gross-total removal of the lesion was achieved in 10 patients (91%), and in 1 patient with a TSM only a near-total (> 90%) resection was possible. Four patients with preoperative visual function defect had a complete recovery, whereas 3 patients experienced a transient worsening of vision, fully recovered within few days. In 3 patients (2 with TSMs and 1 with an OGM), a postoperative CSF leak occurred, requiring a endoscopic surgery for skull base defect repair. Another patient (a case involving a TSM) developed transient diabetes insipidus. The operative time ranged from 6 to 10 hours in the OGM group and from 4.5 to 9 hours in the TSM group. The mean duration of the hospital stay was 13.5 and 10 days in the OGM and TSM groups, respectively. Six patients (3 with OGMs and 3 with TSMs) required a blood transfusion. Surgery-related death occurred in 1 patient with TSM, in whom the tumor was successfully removed. The technique offers a minimally invasive route to the midline anterior skull base, allowing the surgeon to avoid using brain retraction and reducing manipulation of the large vessels and

Pooled analysis of Swedish case-control studies during 1997-2003 and 2007-2009 on meningioma risk associated with the use of mobile and cordless phones.

PubMed

Carlberg, Michael; Hardell, Lennart

2015-06-01

A pooled analysis of two case-control studies on meningioma with patients diagnosed during 1997-2003 and 2007-2009 was conducted. Both genders were included, aged 20-80 and 18-75 years, respectively, at the time of diagnosis. Population-based controls, matched according to age and gender, were enrolled. Exposure was assessed by questionnaire. In the entire study, cases with all brain tumor types were included. The whole reference group was used in the unconditional logistic regression analysis on meningioma, with adjustments for gender, age, year of diagnosis and socio-economic index (SEI). In total, 1,625 meningioma cases and 3,530 controls were analyzed. Overall no association with use of mobile or cordless phones was found. In the fourth quartile of use (>1,436 h) somewhat increased risk was found for mobile phones yielding an odds ratio (OR)=1.2, 95% confidence intervals (CI)=0.9-1.6 and cordless phones OR=1.7, 95% CI=1.3-2.2. Higher risk was calculated in the highest decile (>3,358 h), OR=1.5, 95% CI=0.99-2.1 and OR=2.0, 95% CI=1.4-2.8, respectively. In addition, the longest latency time gave somewhat increased risk for both phone types although the result was not statistically significant. There was no association for ipsilateral use or anatomical tumor location. The present study showed a somewhat increased risk among heavy users of mobile and cordless phones. Since meningioma is generally a slow-growing tumor, longer latency period is necessary for definitive conclusions.

Extracranial-intracranial bypass in medial sphenoid ridge meningioma associated with severe stenosis of the intracranial segments of the internal carotid artery: A case report.

PubMed

Huang, Yabo; Wang, Zhong; Han, Qingdong

2018-06-01

Tumor resection and extracranial-intracranial bypass concerning medial sphenoid ridge meningioma associated with severe stenosis of the internal carotid artery (ICA) of intracranial segments has been rarely presented. Effective treatment as to the complex lesions may be complicated. Tumor resection and cerebrovascular protection should be both taken into consideration. We presented one case of medial sphenoid ridge meningioma associated with severe stenosis of the internal carotid artery of intracranial segments. The patient suffered hyperthyroidism, mirror-image dextrocardia and congenital heart disease atrial septal defect simultaneously. Before the neurosurgical treatment , the colleagues of department of cardiac surgery, anesthesiology and respiratory medicine agreed on our plan of resecting the tumor following the comprehensive evaluation of basal clinical conditions in the patient. For reducing the bleeding intraoperatively, the interventional branch performed digital subtraction angiography(DSA) and found collateral anastomosis between the supplying vessels of left middle meningeal arteries and anterior choroid arteries. No preoperative interventional embolization was determined considering the risk of cerebral ischemia. The following subtotal resection of medial sphenoid ridge meningioma and left extracranial-intracranial bypass were carried out. Additionally, ipsilateral decompressive craniectomy was done. Post-operative imaging Computed tomography (CT), Computed tomography angiography (CTA) and Transcranial Doppler (TCD) indicated subtotal resection of tumor and bypass patency. The patient was discharged with the right limbs of muscle strength of grade IV. The muscle strength of the patient returned to grade V after 6 months of follow-up. Comprehensive treatment of tumor resection and extracranial-intracranial bypass concerning medial sphenoid ridge meningioma associated with severe stenosis of the internal carotid artery of intracranial segments is

Lumbar Drains Decrease the Risk of Postoperative Cerebrospinal Fluid Leak Following Endonasal Endoscopic Surgery for Suprasellar Meningiomas in Patients With High Body Mass Index.

PubMed

Cohen, Salomon; Jones, Samuel H; Dhandapani, Sivashanmugam; Negm, Hazem M; Anand, Vijay K; Schwartz, Theodore H

2018-01-01

Postoperative cerebrospinal fluid (CSF) leak is a persistent, albeit much less prominent, complication following endonasal endoscopic surgery. The pathology with highest risk is suprasellar meningiomas. A postoperative lumbar drain (LD) is used to decrease the risk of CSF leak but is not universally accepted. To compare the rates of postoperative CSF leak between patients with and without LD who underwent endonasal endoscopic surgical resection of suprasellar meningiomas. A consecutive series of newly diagnosed suprasellar meningiomas was drawn from a prospectively acquired database of endonasal endoscopic surgeries at our institution. An intraoperative, preresection LD was placed and left open at 5 cc/h for ∼48 h. In a subset of patients, the LD could not be placed. Rates of postoperative CSF leak were compared between patients with and without an LD. Twenty-five patients underwent endonasal endoscopic surgical resection of suprasellar meningiomas. An LD could not be placed in 2 patients. There were 2 postoperative CSF leaks (8%), both of which occurred in the patients who did not have an LD (P = .0033). The average body mass index (BMI) of the patients in whom the LD could not be placed was 39.1 kg/m2, compared with 27.6 kg/m2 for those in whom the LD could be placed (P = .009). In the subgroup of obese patients (BMI > 30 kg/m2), LD placement was protective against postoperative CSF leak (P = .022). The inability to place an LD in patients with obesity is a risk factor for postoperative CSF leak. An LD may be useful to prevent postoperative CSF leak, particularly in patients with elevated BMI. Copyright © 2017 by the Congress of Neurological Surgeons

IDH1(R132H) mutation causes a less aggressive phenotype and radiosensitizes human malignant glioma cells independent of the oxygenation status.

PubMed

Kessler, Jacqueline; Güttler, Antje; Wichmann, Henri; Rot, Swetlana; Kappler, Matthias; Bache, Matthias; Vordermark, Dirk

2015-09-01

In malignant glioma the presence of the IDH1 mutation (IDH1(R132H)) is associated with better clinical outcome. However, it is unclear whether IDH1 mutation is associated with a less aggressive phenotype or directly linked to increased sensitivity to radiotherapy. We determined the influence of IDH1(R132H) mutant protein on proliferation and growth in 3D culture, migration, cell survival and radiosensitivity in vitro under normoxia (21% O2) and hypoxia (<1% O2) in a panel of human malignant glioma cell lines (U-251MG, U-343MG, LN-229) with stable overexpression of wild-type (IDH1(wt)) and mutated IDH1 (IDH1(R132H)). Overexpression of IDH1(R132H) in glioma cells resulted in slightly decreased cell proliferation, considerably reduced cell migration and caused differences in growth properties in 3D spheroid cultures. Furthermore, IDH1(R132H)-positive cells consistently demonstrated an increased radiosensitivity in human malignant glioma cells U-251MG (DMF10: 1.52, p<0.01 and 1.42, p<0.01), U-343MG (DMF10: 1.78, p<0.01 and 1.75, p<0.01) and LN-229 (DMF10: 1.41, p<0.05 and 1.68, p<0.01) under normoxia and hypoxia, respectively. Our data indicate that IDH1(R132H) mutation causes both a less aggressive biological behavior and direct radiosensitization of human malignant glioma cells. Targeting IDH1 appears to be an attractive approach in combination with radiotherapy. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Complete regression of human malignant mesothelioma xenografts following local injection of midkine promoter-driven oncolytic adenovirus

PubMed Central

Kubo, Shuji; Kawasaki, Yoshiko; Yamaoka, Norie; Tagawa, Masatoshi; Kasahara, Noriyuki; Terada, Nobuyuki; Okamura, Haruki

2010-01-01

Background Malignant mesothelioma is a highly aggressive tumor with poor prognosis. Conventional therapies for mesothelioma are generally non-curative, and new treatment paradigms are urgently needed. We hypothesized that the tumor-specific midkine (Mdk) promoter could confer transcriptional targeting to oncolytic adenoviruses for effective treatment of malignant mesothelioma. Methods We analyzed Mdk expression by quantitative RT-PCR in six human mesothelioma cell lines, and tested Mdk promoter activity by luciferase reporter assay. Based on these data, we constructed a replication-selective oncolytic adenovirus, designated AdMdk-E1-iresTK, which contains an Mdk promoter-driven adenoviral E1 gene and HSV-thymidine kinase (TK) suicide gene, and CMV promoter-driven green fluorescent protein (GFP) marker gene. Selectivity of viral replication and cytolysis were characterized in normal vs. mesothelioma cells in vitro, and intratumoral spread and antitumor efficacy were investigated in vivo. Results Mdk promoter activity was restricted in normal cells, but highly activated in mesothelioma cell lines. AdMdk-E1-iresTK was seen to efficiently replicate, produce viral progeny, and spread in multiple mesothelioma cell lines. Lytic spread of AdMdk-E1-iresTK mediated efficient killing of these mesothelioma cells, and its in vitro cytocidal effect was significantly enhanced by treatment with the prodrug, ganciclovir. Intratumoral injection of AdMdk-E1-iresTK caused complete regression of MESO4 and MSTO human mesothelioma xenografts in athymic mice. In vivo fluorescence imaging demonstrated intratumoral spread of AdMdk-E1-iresTK-derived signals, which vanished after tumor eradication. Conclusions These data indicate that transcriptional targeting of viral replication by the Mdk promoter represents a promising general strategy for oncolytic virotherapy of cancers with upregulated Mdk expression, including malignant mesothelioma. PMID:20635326

Influence of tumor cell proliferation and sex-hormone receptors on effectiveness of radiation therapy for dogs with incompletely resected meningiomas.

PubMed

Théon, A P; Lecouteur, R A; Carr, E A; Griffey, S M

2000-03-01

To assess the influence of tumor cell proliferation and sex-hormone receptors on the efficacy of megavoltage irradiation for dogs with incompletely resected meningiomas. Longitudinal clinical trial. 20 dogs with incompletely resected intracranial meningiomas. Dogs were treated with 48 Gy of radiation administered 3 times per week on an alternate-day schedule of 4 Gy/fraction for 4 weeks, using bilateral parallel-opposed fields. Tumor proliferative fraction measured by immunohistochemical detection of proliferating cell nuclear antigen (PFPCNA index) ranged from 10 to 42% (median, 24%). Progesterone receptor immunoreactivity was detected in 70% of tumors. Estrogen receptor immunoreactivity was not detected. An inverse correlation was found between detection of progesterone receptors and the PFPCNA index. The overall 2-year progression-free survival (PFS) rate was 68%. The only prognostic factor that significantly affected PFS rate was the PFPCNA index. The 2-year PFS was 42% for tumors with a high PFPCNA index (value > or = 24%) and 91% for tumors with a low PFPCNA index (value < 24%). Tumors with a high PFPCNA index were 9.1 times as likely to recur as were tumors with a low PFPCNA index. This study confirms the value of irradiation for dogs with incompletely resected meningiomas. Prognostic value of the PFPCNA index suggests-that duration of treatment and interval from surgery to start of irradiation may affect outcome. Loss of progesterone receptors in some tumors may be responsible for an increase in PFPCNA index and may indirectly affect prognosis after radiation therapy.

Brain tumor - children

MedlinePlus

... children; Neuroglioma - children; Oligodendroglioma - children; Meningioma - children; Cancer - brain tumor (children) ... The cause of primary brain tumors is unknown. Primary brain tumors may ... (spread to nearby areas) Cancerous (malignant) Brain tumors ...

Measurement of the perfusion fraction in brain tumors with intravoxel incoherent motion MR imaging: validation with histopathological vascular density in meningiomas.

PubMed

Togao, Osamu; Hiwatashi, Akio; Yamashita, Koji; Kikuchi, Kazufumi; Momosaka, Daichi; Yoshimoto, Koji; Kuga, Daisuke; Mizoguchi, Masahiro; Suzuki, Satoshi O; Iwaki, Toru; Van Cauteren, Marc; Iihara, Koji; Honda, Hiroshi

2018-05-01

To evaluate the quantification performance of the perfusion fraction (f) measured with intravoxel incoherent motion (IVIM) MR imaging in a comparison with the histological vascular density in meningiomas. 29 consecutive patients with meningioma (59.0 ± 16.8 years old, 8 males and 21 females) who underwent a subsequent surgical resection were examined with both IVIM imaging and a histopathological analysis. IVIM imaging was conducted using a single-shot SE-EPI sequence with 13 b-factors (0, 10, 20, 30, 50, 80, 100, 200, 300, 400, 600, 800, 1000 s mm - 2 ) at 3T. The perfusion fraction (f) was calculated by fitting the IVIM bi-exponential model. The 90-percentile f-value in the tumor region-of-interest (ROI) was defined as the maximum f-value (f-max). Histopathological vascular density (%Vessel) was measured on CD31-immunostainted histopathological specimens. The correlation and agreement between the f-values and %Vessel was assessed. The f-max (15.5 ± 5.5%) showed excellent agreement [intraclass correlation coefficient (ICC) = 0.754] and a significant correlation (r = 0.69, p < 0.0001) with the %Vessel (12.9 ± 9.4%) of the tumors. The Bland-Altman plot analysis showed excellent agreement between the f-max and %Vessel (bias, -2.6%; 95% limits of agreement, from -16.0 to 10.8%). The f-max was not significantly different among the histological subtypes of meningioma. An excellent agreement and a significant correlation were observed between the f-values and %Vessel. The f-value can be used as a noninvasive quantitative imaging measure to directly assess the vascular volume fraction in brain tumors. Advances in knowledge: The f-value measured by IVIM imaging showed a significant correlation and an excellent agreement with the histological vascular density in the meningiomas. The f-value can be used as a noninvasive and quantitative imaging measure to directly assess the volume fraction of capillaries in brain tumors.

Frontobasal Midline Meningiomas: Is It Right To Shed Doubt on the Transcranial Approaches? Updates and Review of the Literature.

PubMed

Ruggeri, Andrea Gennaro; Cappelletti, Martina; Fazzolari, Benedetta; Marotta, Nicola; Delfini, Roberto

2016-04-01

Traditionally, the surgical removal of tuberculum sellae meningioma (TSM) and olfactory groove meningioma (OGM) requires transcranial approaches and microsurgical techniques, but in the last decade endoscopic expanded endonasal approaches have been introduced: transcribriform for OGMs and transtuberculum-transplanum for TSM. A comparative analysis of the literature concerning the two types of surgical treatment of OGMs and TSM is, however, difficult. We conducted a literature search using the PubMed database to compare data for endoscopic and microsurgical techniques in the literature. We also conducted a retrospective analysis of selected cases from our series presenting favorable characteristics for an endoscopic approach, based on the criteria of operability of these lesions as generally accepted in the literature, and we compared the results obtained in these patients with those in the endoscopic literature. We believe that making the sample more homogeneous, the difference between microsurgical technique and endoscopic technique is no longer so striking. A greater radical removal rate, a reduced incidence of cerebrospinal fluid fistula and, especially, the possibility of removing lesions of any size are advantages of transcranial surgery; a higher percentage of improvement in visual outcome and a lower risk of a worsening of a pre-existing deficit or onset of a new deficit are advantages of the endoscopic technique. At present, the microsurgical technique is still the gold standard for the removal of the anterior cranial fossa meningiomas of all sizes, and the endoscopic technique remains a second option in certain cases. Copyright © 2016 Elsevier Inc. All rights reserved.

Electroconvulsive therapy for medication-refractory depression in a patient with ruptured intracranial dermoid cyst, meningioma, and neurofibromatosis.

PubMed

Thukral-Mahajan, Priyanka; Shah, Nilesh; Kalra, Gurvinder; Andrade, Chittaranjan

2017-01-01

Electroconvulsive therapy (ECT) is considered relatively contraindicated in patients with intracranial space-occupying lesions. A 53-year-old male presented with a 5-year history of medication-refractory major depressive disorder. Brain imaging findings suggested the presence of a ruptured dermoid cyst in the transverse sinus and a calcified meningioma in the temporal lobe sulcal space. There was no evidence of mass effect. Neurofibromatosis was the only other clinical condition present. The patient had no clinical neurological deficits. Since the depression was severe and he was suicidal, ECT was advised. There was a substantial improvement after four bilateral and then eight right unilateral brief-pulse ECTs administered on alternate days, thrice weekly. There were no complications associated with ECT. The treatment gains were maintained with maintenance antidepressant medication at a 1-year follow-up. This is probably the first reported case of the use of ECT in a medication-refractory, severely depressed patient with a ruptured intracranial dermoid cyst and with a calcifying meningioma. The results testify to the safety of ECT even in high-risk patients.

Activation of translation complex eIF4F is essential for the genesis and maintenance of the malignant phenotype in human mammary epithelial cells.

PubMed

Avdulov, Svetlana; Li, Shunan; Michalek, Van; Burrichter, David; Peterson, Mark; Perlman, David M; Manivel, J Carlos; Sonenberg, Nahum; Yee, Douglas; Bitterman, Peter B; Polunovsky, Vitaly A

2004-06-01

Common human malignancies acquire derangements of the translation initiation complex, eIF4F, but their functional significance is unknown. Hypophosphorylated 4E-BP proteins negatively regulate eIF4F assembly by sequestering its mRNA cap binding component eIF4E, whereas hyperphosphorylation abrogates this function. We found that breast carcinoma cells harbor increases in the eIF4F constituent eIF4GI and hyperphosphorylation of 4E-BP1 which are two alterations that activate eIF4F assembly. Ectopic expression of eIF4E in human mammary epithelial cells enabled clonal expansion and anchorage-independent growth. Transfer of 4E-BP1 phosphorylation site mutants into breast carcinoma cells suppressed their tumorigenicity, whereas loss of these 4E-BP1 phosphorylation site mutants accompanied spontaneous reversion to a malignant phenotype. Thus, eIF4F activation is an essential component of the malignant phenotype in breast carcinoma.

Human herpes simplex viruses in benign and malignant thyroid tumours.

PubMed

Jensen, Kirk; Patel, Aneeta; Larin, Alexander; Hoperia, Victoria; Saji, Motoyasu; Bauer, Andrew; Yim, Kevin; Hemming, Val; Vasko, Vasyl

2010-06-01

To test the hypothesis that herpes viruses may have a role in thyroid neoplasia, we analysed thyroid tissues from patients with benign (44) and malignant (65) lesions for HSV1 and HSV2 DNA. Confirmatory studies included direct sequencing, analysis of viral gene expression, and activation of viral-inducible signalling pathways. Expression of viral entry receptor nectin-1 was examined in human samples and in cancer cell lines. In vitro experiments were performed to explore the molecular mechanisms underlying thyroid cancer cell susceptibility to HSV. HSV DNA was detected in 43/109 (39.4%) examined samples. HSV capsid protein expression correlated with HSV DNA status. HSV-positive tumours were characterized by activation of virus-inducible signalling such as interferon-beta expression and nuclear NFkappaB expression. Lymphocyte infiltration and oncocytic cellular features were common in HSV-positive tumours. HSV1 was detected with the same frequency in benign and malignant thyroid tumours. HSV2 was significantly associated with papillary thyroid cancer and the presence of lymph node metastases. The expression of HSV entry receptor nectin-1 was increased in thyroid tumours compared to normal thyroid tissue and further increased in papillary thyroid cancer. Nectin-1 expression was detected in all examined thyroid cancer cell lines. Nectin-1 expression in cancer cells correlated with their susceptibility to HSV. Inhibition of PI3K/AKT or MAPK/ERK signalling did not affect the level of nectin-1 expression but decreased thyroid cancer cell susceptibility to HSV. These findings showed that HSV is frequently detected in thyroid cancer. During tumour progression, thyroid cells acquire increased susceptibility to HSV due to increased expression of viral entry mediator nectin-1 and activation of mitogenic signalling in cancer cells.

Identification of miRNA-103 in the Cellular Fraction of Human Peripheral Blood as a Potential Biomarker for Malignant Mesothelioma – A Pilot Study

PubMed Central

Weber, Daniel G.; Johnen, Georg; Bryk, Oleksandr; Jöckel, Karl-Heinz; Brüning, Thomas

2012-01-01

Background To date, no biomarkers with reasonable sensitivity and specificity for the early detection of malignant mesothelioma have been described. The use of microRNAs (miRNAs) as minimally-invasive biomarkers has opened new opportunities for the diagnosis of cancer, primarily because they exhibit tumor-specific expression profiles and have been commonly observed in blood of both cancer patients and healthy controls. The aim of this pilot study was to identify miRNAs in the cellular fraction of human peripheral blood as potential novel biomarkers for the detection of malignant mesothelioma. Methodology/Principal Findings Using oligonucleotide microarrays for biomarker identification the miRNA levels in the cellular fraction of human peripheral blood of mesothelioma patients and asbestos-exposed controls were analyzed. Using a threefold expression change in combination with a significance level of p<0.05, miR-103 was identified as a potential biomarker for malignant mesothelioma. Quantitative real-time PCR (qRT-PCR) was used for validation of miR-103 in 23 malignant mesothelioma patients, 17 asbestos-exposed controls, and 25 controls from the general population. For discrimination of mesothelioma patients from asbestos-exposed controls a sensitivity of 83% and a specificity of 71% were calculated, and for discrimination of mesothelioma patients from the general population a sensitivity of 78% and a specificity of 76%. Conclusions/Significance The results of this pilot study show that miR-103 is characterized by a promising sensitivity and specificity and might be a potential minimally-invasive biomarker for the diagnosis of mesothelioma. In addition, our results support the concept of using the cellular fraction of human blood for biomarker discovery. However, for early detection of malignant mesothelioma the feasibility of miR-103 alone or in combination with other biomarkers needs to be analyzed in a prospective study. PMID:22253921

Inhibition of WNT signaling reduces differentiation and induces sensitivity to doxorubicin in human malignant neuroblastoma SH-SY5Y cells.

PubMed

Suebsoonthron, Junjira; Jaroonwitchawan, Thiranut; Yamabhai, Montarop; Noisa, Parinya

2017-06-01

Neuroblastoma is one of the most common cancers in infancy, arising from the neuroblasts during embryonic development. This cancer is difficult to treat and resistance to chemotherapy is often found; therefore, clinical trials of novel therapeutic approaches, such as targeted-cancer signaling, could be an alternative for a better treatment. WNT signaling plays significant roles in the survival, proliferation, and differentiation of human neuroblastoma. In this report, WNT signaling of a malignant human neuroblastoma cell line, SH-SY5Y cells, was inhibited by XAV939, a specific inhibitor of the Tankyrase enzyme. XAV939 treatment led to the reduction of β-catenin within the cells, confirming its inhibitory effect of WNT. The inhibition of WNT signaling by XAV939 did not affect cell morphology, survival, and proliferation; however, the differentiation and sensitivity to anticancer drugs of human neuroblastoma cells were altered. The treatment of XAV939 resulted in the downregulation of mature neuronal markers, including β-tubulin III, PHOX2A, and PHOX2B, whereas neural progenitor markers (PAX6, TFAP2α, and SLUG) were upregulated. In addition, the combination of XAV939 significantly enhanced the sensitivity of SH-SY5Y and IMR-32 cells to doxorubicin in both 2D and 3D culture systems. Microarray gene expression profiling suggested numbers of candidate target genes of WNT inhibition by XAV939, in particular, p21, p53, ubiquitin C, ZBED8, MDM2, CASP3, and FZD1, and this explained the enhanced sensitivity of SH-SY5Y cells to doxorubicin. Altogether, these results proposed that the altered differentiation of human malignant neuroblastoma cells by inhibiting WNT signaling sensitized the cells to anticancer drugs. This approach could thus serve as an effective treatment option for aggressive brain malignancy.

Microspectroscopic Analysis Of HpD Fluorescence In Bioptic Samples From Human Pre-Malignant And Malignant Lesions Of The Skin

NASA Astrophysics Data System (ADS)

Bottiroli, G.; Dell'Acqua, R.; Jucci, A.; Ricevuti, G.; Sacchi, A. S.

1987-07-01

Microfluorometric analysis was performed on bioptic samples of pre-malignant and malignant cutanous lesions present in the same patients, 48 h after i.v. injection of HpD. Data obtained indicate that actinic keratosis and squamous celle carcinoma show a preferential accumulation if compared to normal skin. The two lesions differ for both intensity and spectral shape of HpD fluorescence. This difference is correlated with a different clinical response to HpD laser phototherapy.

Short Chain Fatty Acids (SCFA) Reprogram Gene Expression in Human Malignant Epithelial and Lymphoid Cells

PubMed Central

Astakhova, Lidiia; Ngara, Mtakai; Babich, Olga; Prosekov, Aleksandr; Asyakina, Lyudmila; Dyshlyuk, Lyubov; Midtvedt, Tore; Zhou, Xiaoying; Ernberg, Ingemar; Matskova, Liudmila

2016-01-01

The effect of short chain fatty acids (SCFAs) on gene expression in human, malignant cell lines was investigated, with a focus on signaling pathways. The commensal microbial flora produce high levels of SCFAs with established physiologic effects in humans. The most abundant SCFA metabolite in the human microflora is n-butyric acid. It is well known to activate endogenous latent Epstein-Barr virus (EBV), that was used as a reference read out system and extended to EBV+ epithelial cancer cell lines. N-butyric acid and its salt induced inflammatory and apoptotic responses in tumor cells of epithelial and lymphoid origin. Epithelial cell migration was inhibited. The n-butyric gene activation was reduced by knock-down of the cell membrane transporters MCT-1 and -4 by siRNA. N-butyric acid show biologically significant effects on several important cellular functions, also with relevance for tumor cell phenotype. PMID:27441625

Transcription analysis in the MeLiM swine model identifies RACK1 as a potential marker of malignancy for human melanocytic proliferation

PubMed Central

Egidy, Giorgia; Julé, Sophia; Bossé, Philippe; Bernex, Florence; Geffrotin, Claudine; Vincent-Naulleau, Silvia; Horak, Vratislav; Sastre-Garau, Xavier; Panthier, Jean-Jacques

2008-01-01

Background Metastatic melanoma is a severe disease. Few experimental animal models of metastatic melanoma exist. MeLiM minipigs exhibit spontaneous melanoma. Cutaneous and metastatic lesions are histologically similar to human's. However, most of them eventually spontaneously regress. Our purpose was to investigate whether the MeLiM model could reveal markers of malignancy in human melanocytic proliferations. Results We compared the serial analysis of gene expression (SAGE) between normal pig skin melanocytes and melanoma cells from an early pulmonary metastasis of MeLiM minipigs. Tag identification revealed 55 regulated genes, including GNB2L1 which was found upregulated in the melanoma library. In situ hybridisation confirmed GNB2L1 overexpression in MeLiM melanocytic lesions. GNB2L1 encodes the adaptor protein RACK1, recently shown to influence melanoma cell lines tumorigenicity. We studied the expression of RACK1 by immunofluorescence and confocal microscopy in tissues specimens of normal skin, in cutaneous and metastatic melanoma developped in MeLiM minipigs and in human patients. In pig and human samples, the results were similar. RACK1 protein was not detected in normal epidermal melanocytes. By contrast, RACK1 signal was highly increased in the cytoplasm of all melanocytic cells of superficial spreading melanoma, recurrent dermal lesions and metastatic melanoma. RACK1 partially colocalised with activated PKCαβ. In pig metastases, additional nuclear RACK1 did not associate to BDNF expression. In human nevi, the RACK1 signal was low. Conclusion RACK1 overexpression detected in situ in human melanoma specimens characterized cutaneous and metastatic melanoma raising the possibility that RACK1 can be a potential marker of malignancy in human melanoma. The MeLiM strain provides a relevant model for exploring mechanisms of melanocytic malignant transformation in humans. This study may contribute to a better understanding of melanoma pathophysiology and to

Immunohistochemical study on the expression of matrix metalloproteinase 2 and high-risk human papilloma virus in the malignant progression of papillomas

PubMed Central

Lee, Ho-Jin

2013-01-01

Objectives Papilloma frequently develops as a benign tumor of the head and neck area, but its potential for malignant transformation has yet to be studied. This study aims to provide basic information for papillomas using the immunohistochemical staining of matrix metalloproteinase 2 (MMP-2) and human papilloma virus (HPV) 16 and 18. Materials and Methods To evaluate the malignant transformation of papillomas, the selected tissue samples were serially diagnosed with pre-cancerous papilloma (with epithelial dysplasia, pseudo-epitheliomatous hyperplasia) or malignant lesion (squamous cell carcinoma, SCC) after the first diagnosis (squamous papilloma, inverted papilloma). The selected tissues were stained with an antibody to MMP-2 and HPV 16-E7, HPV 18-L1. A statistical analysis was performed according to each transformation step. Results The epithelial layer of papilloma and pre-cancerous papilloma lesions had a similar MMP-2 expression, but that of the malignant lesion had a significantly increased MMP-2 expression. HPV 16 and 18 infection rates were 28.6%, 33.3% and 63.6% in papillomas, pre-cancerous papilloma lesions, and SCC. Conclusions A relatively high MMP-2 expression and HPV 16 or 18 infection of papillomas may be associated with early events in the multistep processes of malignant transformation of papillomas. PMID:24471049

Clinical multifactorial analysis of early postoperative seizures in elderly patients following meningioma resection

PubMed Central

ZHANG, BO; WANG, DAN; GUO, YUNBAO; YU, JINLU

2015-01-01

The aim of the present study was to identify the major factors correlated with early postoperative seizures in elderly patients who had undergone a meningioma resection, and subsequently, to develop a logistic regression equation for assessing the seizures risk. Fourteen factors possibly correlated with early postoperative seizures in a cohort of 209 elderly patients who had undergone meningioma resection, as analyzed by multifactorial stepwise logistic regression. Phenobarbital sodium (0.1 g, intramuscularly) was administered to all 209 patients 30 min prior to undergoing surgery. All the patients had no previous history of seizures. The correlation of the 14 clinical factors (gender, tumor site, dyskinesia, peritumoral brain edema (PTBE), tumor diameter, pre- and postoperative prophylaxes, surgery time, tumor adhesion, circumscription, blood supply, intraoperative transfusion, original site of the tumor and dysphasia) was assessed in association with the risk for post-operative seizures. Tumor diameter, postoperative prophylactic antiepileptic drug (PPAD) administration, PTBE and tumor site were entered as risk factors into a mathematical regression model. The odds ratio (OR) of the tumor diameter was >1, and PPAD administration showed an OR >1, relative to a non-prophylactic group. A logistic regression equation was obtained and the sensitivity, specificity and misdiagnosis rates were 91.4, 74.3 and 25.7%, respectively. Tumor diameter, PPAD administration, PTBE and tumor site were closely correlated with early postoperative seizures; PTBE and PPAD administration were risk and protective factors, respectively. PMID:26137257

RNA-based analysis of two SMARCB1 mutations associated with familial schwannomatosis with meningiomas.

PubMed

Melean, German; Velasco, Ana; Hernández-Imaz, Elisabete; Rodríguez-Álvarez, Francisco Javier; Martín, Yolanda; Valero, Ana; Hernández-Chico, Concepción

2012-08-01

Germline mutations in the SMARCB1 gene cause familial schwannomatosis, a condition characterized by the presence of multiple schwannomas, although mutations in SMARCB1 have also been associated with rhadboid tumor predisposition syndrome 1 (RTPS1). Both schwannomatosis and RTPS1 are autosomal dominant conditions that predispose individuals to develop distinct types of tumors. We clinically and genetically characterized two families with schwannomatosis associated with SMARCB1 mutations. Eight affected members of these families developed different numbers of schwannomas and/or meningiomas at distinct ages, evidence that meningiomas are variably expressed in this condition. We identified two germline mutations in SMARCB1 associated with the familial disease, c.233-1G>A and the novel c.207_208dupTA mutation, which both proved to affect the main SMARCB1 isoforms at the RNA level distinctly. Interestingly, the c.207_208dupTA mutation had no effect on the coding sequence, pre-mRNA splicing or the level of expression of the SMARCB1 isoform 2. Furthermore, SMARCB1 isoforms harboring a premature termination codon were largely eliminated via the nonsense-mediated mRNA decay pathway. Our results highlight the importance of RNA-based studies to characterize SMARCB1 germline mutations in order to determine their impact on protein expression and gain further insight into the genetic basis of conditions associated with SMARCB1 mutations.

P16INK4a MEDIATED SUPPRESSION OF TELOMERASE IN NORMAL AND MALIGNANT HUMAN BREAST CELLS

PubMed Central

Bazarov, Alexey V.; van Sluis, Marjolein; Hines, Curtis; Bassett, Ekaterina; Beliveau, Alain; Campeau, Eric; Mukhopadhyay, Rituparna; Lee, Won Jae; Melodyev, Sonya; Zaslavsky, Yuri; Lee, Leonard; Rodier, Francis; Chicas, Agustin; Lowe, Scott W.; Benhattar, Jean; Ren, Bing; Campisi, Judith; Yaswen, Paul

2010-01-01

Summary The cyclin-dependent kinase inhibitor p16INK4a (CDKN2A) is an important tumor-suppressor gene frequently inactivated in human tumors. p16 suppresses the development of cancer by triggering an irreversible arrest of cell proliferation termed cellular senescence. Here, we describe another anti-oncogenic function of p16 in addition to its ability to halt cell cycle progression. We show that transient expression of p16 stably represses the hTERT gene, encoding the catalytic subunit of telomerase, in both normal and malignant breast epithelial cells. Short-term p16 expression increases the amount of histone H3 trimethylated on lysine 27 (H3K27) bound to the hTERT promoter, resulting in transcriptional silencing, likely mediated by polycomb complexes. Our results indicate that transient p16 exposure may prevent malignant progression in dividing cells by irreversible repression of genes, such as hTERT, whose activity is necessary for extensive self-renewal. PMID:20569236

The role of CD133 in normal human prostate stem cells and malignant cancer-initiating cells.

PubMed

Vander Griend, Donald J; Karthaus, Wouter L; Dalrymple, Susan; Meeker, Alan; DeMarzo, Angelo M; Isaacs, John T

2008-12-01

Resolving the specific cell of origin for prostate cancer is critical to define rational targets for therapeutic intervention and requires the isolation and characterization of both normal human prostate stem cells and prostate cancer-initiating cells (CIC). Single epithelial cells from fresh normal human prostate tissue and prostate epithelial cell (PrEC) cultures derived from them were evaluated for the presence of subpopulations expressing stem cell markers and exhibiting stem-like growth characteristics. When epithelial cell suspensions containing cells expressing the stem cell marker CD133+ are inoculated in vivo, regeneration of stratified human prostate glands requires inductive prostate stromal cells. PrEC cultures contain a small subpopulation of CD133+ cells, and fluorescence-activated cell sorting-purified CD133+ PrECs self-renew and regenerate cell populations expressing markers of transit-amplifying cells (DeltaNp63), intermediate cells (prostate stem cell antigen), and neuroendocrine cells (CD56). Using a series of CD133 monoclonal antibodies, attachment and growth of CD133+ PrECs requires surface expression of full-length glycosylated CD133 protein. Within a series of androgen receptor-positive (AR+) human prostate cancer cell lines, CD133+ cells are present at a low frequency, self-renew, express AR, generate phenotypically heterogeneous progeny negative for CD133, and possess an unlimited proliferative capacity, consistent with CD133+ cells being CICs. Unlike normal adult prostate stem cells, prostate CICs are AR+ and do not require functional CD133. This suggests that (a) AR-expressing prostate CICs are derived from a malignantly transformed intermediate cell that acquires "stem-like activity" and not from a malignantly transformed normal stem cell and (b) AR signaling pathways are a therapeutic target for prostate CICs.

Epidemiology of primary brain tumors in the Middle Eastern population in California, USA 2001-2005.

PubMed

Nasseri, Kiumarss; Mills, John R

2009-01-01

The fast growing Middle Eastern (ME) population has rarely been studied in the U.S.. The purpose of this study was to compare the epidemiology of primary brain tumors in this ethnic population with the non-Hispanic, non-Middle Eastern White (NHNMW) in California. ME cases were identified by surname in the California cancer registry and ME population estimates were based on ancestry. Data for 683 cases of primary brain tumors (429 benign, 238 malignant, 16 uncertain) in the ME and 15,589 cases (8352 benign, 6812 malignant, 425 uncertain) in the NHNMW were available for this study. ME patients were significantly (p < 0.05) younger and their age-adjusted incidence rates per 100,000 for benign tumors of 10.0 in men and 17.6 in women were higher than similar rates of 7.3 and 10.6 in the NHNMW group (p < 0.05). Rates for malignant tumors were similar. Meningioma was the main histology responsible for the observed increase in patients over 40 years of age. Also increased were benign tumors of the pituitary and pineal glands. The overall mortality in patients with benign tumors was significantly lower than malignant tumors. This study presents a significantly high incidence of benign meningioma in the ME population in California. This may be due to higher susceptibility or exposure of this ethnic group to the risk factor(s) for this neoplasm. Considering the reported causal association of benign meningioma with childhood radiation exposure from Israel, exposure to this risk factor in this ethnic group needs to be evaluated in future studies.

Update on non-acquired immunodeficiency syndrome-defining malignancies.

PubMed

Chiao, Elizabeth Y; Krown, Susan E

2003-09-01

Since the introduction of highly active antiretroviral therapy (HAART), the natural history of human immunodeficiency virus (HIV) infection has changed. Early in the acquired immunodeficiency syndrome (AIDS) epidemic, epidemiologic studies showed that HIV-infected patients were at higher risk for developing specific AIDS-defining malignancies. More recent studies linking HIV/AIDS databases to cancer registries have shown that HIV-infected patients are also at higher risk of developing non-AIDS-defining malignancies. We review the most recent data regarding clinical presentation, pathology, and treatment outcomes for these non-AIDS-defining malignancies. Recent large cohort studies linking HIV/AIDS databases to cancer registries have shown that HIV-infected patients are also at higher risk of developing non-AIDS-defining malignancies. Besides anal cancer and Hodgkin disease, the cohort studies have identified other malignancies that appear to occur at a higher rate in the HIV-infected population as compared with the general population. These malignancies include lung cancer, skin cancer, germ cell tumors, leiomyosarcomas, cancers of the head and neck, conjunctival cancer, multiple myeloma, and leukemias. As the epidemiology of non-AIDS-defining malignancies continues to evolve, it is unclear whether the appropriate treatments and outcomes for these or other malignancies are changed for HIV-infected patients treated with HAART.

Influence of zinc deficiency on AKT-MDM2-P53 signaling axes in normal and malignant human prostate cells

USDA-ARS?s Scientific Manuscript database

With prostate being the highest zinc-accumulating tissue before the onset of cancer, the effects of physiologic levels of zinc on Akt-Mdm2-p53 and Akt-p21 signaling axes in human normal prostate epithelial cells (PrEC) and malignant prostate LNCaP cells were examined. Cells were cultured for 6 d in...

Estimation of the epidemiological burden of human papillomavirus-related cancers and non-malignant diseases in men in Europe: a review

PubMed Central

2012-01-01

Background The role of human papillomavirus (HPV) in malignant and non-malignant genital diseases in women is well known and the corresponding epidemiological burden has been widely described. However, less is known about the role of HPV in anal, penile and head and neck cancer, and the burden of malignant and non-malignant HPV-related diseases in men. The objective of this review is to estimate the epidemiological burden of HPV-related cancers and non-malignant diseases in men in Europe. Methods The annual number of new HPV-related cancers in men in Europe was estimated using Eurostat population data and applying cancer incidence rates published by the International Agency for Research on Cancer. The number of cancer cases attributable to HPV, and specifically to HPV16/18, was calculated based on the most relevant prevalence estimates. The annual number of new cases of genital warts was calculated from the most robust European studies; and latest HPV6/11 prevalence estimates were then applied. A literature review was also performed to retrieve exhaustive data on HPV infection at all anatomical sites under study, as well as incidence and prevalence of external genital warts, recurrent respiratory papillomatosis and HPV-related cancer trends in men in Europe. Results A total of 72, 694 new cancer cases at HPV-related anatomical sites were estimated to occur each year in men in Europe. 17,403 of these cancer cases could be attributable to HPV, with 15,497 of them specifically attributable to HPV16/18. In addition, between 286,682 and 325,722 new cases of genital warts attributable to HPV6/11were estimated to occur annually in men in Europe. Conclusions The overall estimated epidemiological burden of HPV-related cancers and non-malignant diseases is high in men in Europe. Approximately 30% of all new cancer cases attributable to HPV16/18 that occur yearly in Europe were estimated to occur in men. As in women, the vast majority of HPV-positive cancer in men is related

Elevated osteopontin and thrombospondin expression identifies malignant human breast carcinoma but is not indicative of metastatic status

PubMed Central

Wang-Rodriguez, Jessica; Urquidi, Virginia; Rivard, Amber; Goodison, Steve

2003-01-01

Background Our previous characterization of a human breast tumor metastasis model identified several candidate metastasis genes. The expression of osteopontin (OPN) correlated with the metastatic phenotype, whereas thrombospondin-1 (TSP-1) and tyrosinase-related protein-1 (TYRP-1) correlated with the nonmetastatic phenotype of independent MDA-MB-435 cell lines implanted orthotopically into athymic mice. The aim of the present study was to examine the cellular distribution of these molecules in human breast tissue and to determine whether the relative expression level of these three genes is associated with human breast tumor metastasis. Methods Sixty-eight fresh, frozen specimens including 31 primary infiltrating ductal carcinomas, 22 nodal metastases, 10 fibroadenomas, and five normal breast tissues were evaluated for OPN expression, TSP-1 expression and TYRP-1 expression. Immunohistochemistry was performed to monitor the cellular distribution and to qualitatively assess expression. Quantitative analysis was achieved by enrichment of breast epithelial cells using laser-capture microdissection and subsequent real-time, quantitative PCR. Results The epithelial components of the breast tissue were the source of OPN and TSP-1 expression, whereas TYRP-1 was present in both the epithelial and stromal components. Both OPN and TSP-1 expression were significantly higher in malignant epithelial sources over normal and benign epithelial sources, but no difference in expression levels was evident between primary tumors with or without metastases, nor between primary and metastatic carcinomas. Conclusion Elevated expression of OPN and TSP-1 may play a role in the pathogenesis of breast cancer. The multiplex analysis of these molecules may enhance our ability to diagnose and/or prognosticate human breast malignancy. PMID:12927044

Sleep Quality, Sleep EEG Pattern, Mental Well-Being and Cortisol Secretion in Patients with Ruptured Aneurysm Post-Treatment: A Comparison with Post-Surgery Meningioma Patients and Controls.

PubMed

Gerber, Markus; Colledge, Flora; Pühse, Uwe; Holsboer-Trachsler, Edith; Zimmerer, Stefan; Brand, Serge

2016-01-01

Although the chance of surviving an aneurysmal subarachnoid haemorrhage (aSAH) has increased steadily, disturbed sleep and persistent psychological complaints are frequently experienced post-ictus. To date, however, few studies have sought to determine whether physiological parameters, such as objectively measured sleep and cortisol secretion, interrelate significantly with low sleep quality and psychological complaints such as depression. Furthermore, there is little evidence as to whether post-ictal complaints differ between aSAH patients and other groups who have experienced stressful medical intervention. Data on objective and subjective sleep, sleep-related dysfunctional cognitions, psychological functioning and cortisol secretion were collected from 15 patients who had undergone medical intervention for aSAH. Data were also collected from a group of 16 individuals who had undergone surgery for a meningioma and a third group made up of 17 healthy participants. aSAH patients and meningioma patients had significantly poorer subjective sleep than healthy controls and reported more sleep-related dysfunctional cognitions and hypochondriacal beliefs. They also had a significantly higher morning cortisol response. Finally, a non-significant trend was found showing that aSAH patients and meningioma patients reported poorer psychological functioning than healthy controls. Following treatment, aSAH patients and meningioma patients experience poorer subjective sleep and some differences in objectively measured sleep, which might be attributable to increased sleep-related dysfunctional cognitions and poorer overall psychological functioning. Differences in cortisol production were also observed, suggesting that some physiological imbalances are still present post-ictus. © 2016 S. Karger AG, Basel.

Methylene Blue as a Diagnostic Aid in the Early Detection of Potentially Malignant and Malignant Lesions of Oral Mucosa.

PubMed

Lejoy, Abraham; Arpita, Rai; Krishna, Burde; Venkatesh, Naikmasur

2016-05-01

In vivo stains are the prompt resources, which have emerged in recent years to aid as clinical diagnostic tools in detecting early potentially malignant and malignant lesions. Toluidine blue, by its property of retaining in the increased DNA and RNA cellular activity areas, aids in delineating the suspicious areas. However, it is hazardous if swallowed, and has been shown to have toxicity to fibroblasts. Methylene blue has a similar chemical structure and exhibits similar physicochemical properties as toluidine blue. It is less toxic to the human body and has recently been proposed for screening some gastrointestinal or prostate tumors. The application of this material in detecting oral lesions has so far not been addressed. The objective of this study was to evaluate the sensitivity and reliability of in vivo staining with methylene blue as a diagnostic adjunct in screening for oral malignant or potentially malignant lesions. The present study involved the examination of 75 patients suspected of having oral malignant or potentially malignant lesions by methylene blue staining. The results of methylene blue uptake were compared with a simultaneous biopsy of these lesions. The overall sensitivity was 95% (100% for malignancy and 92% for potentially malignant lesions) and specificity was 70%. The positive predictive value was 91% and negative predictive value of 80% was observed in the study. We consider that methylene blue staining is a useful diagnostic adjunct in a large, community-based oral cancer screening program for high-risk individuals.

Expression of metalloprotease insulin-degrading enzyme insulysin in normal and malignant human tissues.

PubMed

Yfanti, Christina; Mengele, Karin; Gkazepis, Apostolos; Weirich, Gregor; Giersig, Cecylia; Kuo, Wen-Liang; Tang, Wei-Jen; Rosner, Marsha; Schmitt, Manfred

2008-10-01

Insulin-degrading enzyme (IDE, insulysin, insulinase; EC 3.4.22.11), a thiol metalloendopeptidase, is involved in intracellular degradation of insulin, thereby inhibiting its translocation and accumulation to the nucleus. Recently, protein expression of IDE has been demonstrated in the epithelial ducts of normal breast and breast cancer tissue. Utilizing four different antibodies generated against different epitopes of the IDE molecule, we performed Western blot analysis and immunohistochemical staining on several normal human tissues, on a plethora of tumor cell lines of different tissue origin, and on malignant breast and ovarian tissue. Applying the four IDE-directed antibodies, we demonstrated IDE expression at the protein level, by means of immunoblotting and immunocytochemistry, in each of the tumor cell lines analyzed. Insulin-degrading enzyme protein expression was found in normal tissues of the kidney, liver, lung, brain, breast and skeletal muscle, as well as in breast and ovarian cancer tissues. Immunohistochemical visualization of IDE indicated cytoplasmic localization of IDE in each of the cell lines and tissues assessed. In conclusion, we performed for the first time a wide-ranging survey on IDE protein expression in normal and malignant tissues and cells thus extending our knowledge on the cellular and tissue distribution of IDE, an enzyme which to date has mainly been studied in connection with Alzheimer's disease and diabetes but not in cancer.

Deregulation of cancer-related miRNAs is a common event in both benign and malignant human breast tumors.

PubMed

Tahiri, Andliena; Leivonen, Suvi-Katri; Lüders, Torben; Steinfeld, Israel; Ragle Aure, Miriam; Geisler, Jürgen; Mäkelä, Rami; Nord, Silje; Riis, Margit L H; Yakhini, Zohar; Kleivi Sahlberg, Kristine; Børresen-Dale, Anne-Lise; Perälä, Merja; Bukholm, Ida R K; Kristensen, Vessela N

2014-01-01

MicroRNAs (miRNAs) are endogenous non-coding RNAs, which play an essential role in the regulation of gene expression during carcinogenesis. The role of miRNAs in breast cancer has been thoroughly investigated, and although many miRNAs are identified as cancer related, little is known about their involvement in benign tumors. In this study, we investigated miRNA expression profiles in the two most common types of human benign tumors (fibroadenoma/fibroadenomatosis) and in malignant breast tumors and explored their role as oncomirs and tumor suppressor miRNAs. Here, we identified 33 miRNAs with similar deregulated expression in both benign and malignant tumors compared with the expression levels of those in normal tissue, including breast cancer-related miRNAs such as let-7, miR-21 and miR-155. Additionally, messenger RNA (mRNA) expression profiles were obtained for some of the same samples. Using integrated mRNA/miRNA expression analysis, we observed that overexpression of certain miRNAs co-occurred with a significant downregulation of their candidate target mRNAs in both benign and malignant tumors. In support of these findings, in vitro functional screening of the downregulated miRNAs in non-malignant and breast cancer cell lines identified several possible tumor suppressor miRNAs, including miR-193b, miR-193a-3p, miR-126, miR-134, miR-132, miR-486-5p, miR-886-3p, miR-195 and miR-497, showing reduced growth when re-expressed in cancer cells. The finding of deregulated expression of oncomirs and tumor suppressor miRNAs in benign breast tumors is intriguing, indicating that they may play a role in proliferation. A role of cancer-related miRNAs in the early phases of carcinogenesis and malignant transformation can, therefore, not be ruled out.

Knowledge of human papillomavirus and its association with head and neck benign and malignant lesions in a group of dental patients in pakistan.

PubMed

Gichki, Abdul Samad; Buajeeb, Waranun; Doungudomdacha, Sombhun; Khovidhunkit, Siribang-On Pibooniyom

2015-01-01

Human papillomaviruses (HPVs) remain a serious world health problem due to their association with cervical and head and neck cancers. While over 100 HPV types have been identified, only a few subtypes are associated with malignancies. HPV 16 and 18 are the most prevalent oncogenic types in head and neck cancers. Although it has been proven that some subsets of benign and malignant head and neck lesions are associated with HPV, the general population have very little awareness and knowledge of their association with HPV. Therefore, the purpose of this study was to determine the knowledge of HPV and its links with head and neck benign and malignant lesions in a group of Pakistani dental patients who attended the Dental Department of the Sandeman provincial hospital in Quetta, Pakistan. One hundred and ninety-two patients were recruited and requested to answer a questionnaire. It was revealed that there was a low level of knowledge about HPV and its association with head and neck benign and malignant lesions among the participants. This result suggested that more education regarding the relationship of HPV in inducing head and neck benign and malignant lesions is required in this group of patients.

Deep sequencing of the small RNA transcriptome of normal and malignant human B cells identifies hundreds of novel microRNAs

PubMed Central

Jima, Dereje D.; Zhang, Jenny; Jacobs, Cassandra; Richards, Kristy L.; Dunphy, Cherie H.; Choi, William W. L.; Yan Au, Wing; Srivastava, Gopesh; Czader, Magdalena B.; Rizzieri, David A.; Lagoo, Anand S.; Lugar, Patricia L.; Mann, Karen P.; Flowers, Christopher R.; Bernal-Mizrachi, Leon; Naresh, Kikkeri N.; Evens, Andrew M.; Gordon, Leo I.; Luftig, Micah; Friedman, Daphne R.; Weinberg, J. Brice; Thompson, Michael A.; Gill, Javed I.; Liu, Qingquan; How, Tam; Grubor, Vladimir; Gao, Yuan; Patel, Amee; Wu, Han; Zhu, Jun; Blobe, Gerard C.; Lipsky, Peter E.; Chadburn, Amy

2010-01-01

A role for microRNA (miRNA) has been recognized in nearly every biologic system examined thus far. A complete delineation of their role must be preceded by the identification of all miRNAs present in any system. We elucidated the complete small RNA transcriptome of normal and malignant B cells through deep sequencing of 31 normal and malignant human B-cell samples that comprise the spectrum of B-cell differentiation and common malignant phenotypes. We identified the expression of 333 known miRNAs, which is more than twice the number previously recognized in any tissue type. We further identified the expression of 286 candidate novel miRNAs in normal and malignant B cells. These miRNAs were validated at a high rate (92%) using quantitative polymerase chain reaction, and we demonstrated their application in the distinction of clinically relevant subgroups of lymphoma. We further demonstrated that a novel miRNA cluster, previously annotated as a hypothetical gene LOC100130622, contains 6 novel miRNAs that regulate the transforming growth factor-β pathway. Thus, our work suggests that more than a third of the miRNAs present in most cellular types are currently unknown and that these miRNAs may regulate important cellular functions. PMID:20733160

Microsurgical resection of skull base meningioma-expanding the operative corridor.

PubMed

Raheja, Amol; Couldwell, William T

2016-11-01

A better understanding of surgical anatomy, marked improvement in illumination devices, provision of improved hemostatic agents, greater availability of more precise surgical instruments, and better modalities for skull base reconstruction have led to an inevitable evolution of skull base neurosurgery. For the past few decades, many skull base neurosurgeons have worked relentlessly to improve the surgical approach and trajectory for the expansion of operative corridor. With the advent of newer techniques and their rapid adaptation, it is foundational, especially for young neurosurgeons, to understand the basics and nuances of modifications of traditional neurosurgical approaches. The goal of this topic review is to discuss the evolution of, concepts in, and technical nuances regarding the operative corridor expansion in the field of skull base surgery for intracranial meningioma as they pertain to achieving optimal functional outcome.

Long-term low-dose α-particle enhanced the potential of malignant transformation in human bronchial epithelial cells through MAPK/Akt pathway

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, Weili; Xiao, Linlin; Dong, Chen

2014-05-09

Highlights: • Multi-exposures of 25 mGy α-ray enhanced cell proliferation, adhesion, and invasion. • MAPK/Akt but not JNK/P66 was positively correlated with cell invasive phenotypes. • LDR of α-irradiation triggers cell malignant transformation through MAPK/Akt. - Abstract: Since the wide usage of ionizing radiation, the cancer risk of low dose radiation (LDR) (<0.1 Gy) has become attractive for a long time. However, most results are derived from epidemiologic studies on atomic-bomb survivors and nuclear accidents surrounding population, and the molecular mechanism of this risk is elusive. To explore the potential of a long-term LDR-induced malignant transformation, human bronchial epithelial cellsmore » Beas-2B were fractionally irradiated with 0.025 Gy α-particles for 8 times in total and then further cultured for 1–2 months. It was found that the cell proliferation, the abilities of adhesion and invasion, and the protein expressions of p-ERK, p-Akt, especially p-P38 were not only increased in the multiply-irradiated cells but also in their offspring 1–2 months after the final exposure, indicating high potentiality of cell malignant transformation. On opposite, the expressions of p-JNK and p-P66 were diminished in the subcultures of irradiated cells and thus may play a role of negative regulation in canceration. When the cells were transferred with p38 siRNA, the LDR-induced enhancements of cell adhesion and invasion were significantly reduced. These findings suggest that long-term LDR of α-particles could enhance the potential of malignant transformation incidence in human bronchial epithelial cells through MAPK/Akt pathway.« less

Fractionated Stereotactic Radiotherapy Treatment of Cavernous Sinus Meningiomas: A Study of 100 Cases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Litre, Claude Fabien; Colin, Philippe; Noudel, Remy

Purpose: We discuss our experiences with fractionated stereotactic radiotherapy (FSR) in the treatment of cavernous sinus meningiomas. Methods and Materials: From 1995 to 2006, we monitored 100 patients diagnosed with cavernous sinus meningiomas; 84 female and 16 male patients were included. The mean patient age was 56 years. The most common symptoms were a reduction in visual acuity (57%), diplopia (50%), exophthalmy (30%), and trigeminal neuralgia (34%). Surgery was initially performed on 26 patients. All patients were treated with FSR. A total of 45 Gy was administered to the lesion, with 5 fractions of 1.8 Gy completed each week. Patientmore » treatment was performed using a Varian Clinac linear accelerator used for cranial treatments and a micro-multileaf collimator. Results: No side effects were reported. Mean follow-up period was 33 months, with 20% of patients undergoing follow-up evaluation of more than 4 years later. The tumor control rate at 3 years was 94%. Three patients required microsurgical intervention because FSR proved ineffective. In terms of functional symptoms, an 81% improvement was observed in patients suffering from exophthalmy, with 46% of these patients being restored to full health. A 52% improvement was observed in diplopia, together with a 67% improvement in visual acuity and a 50% improvement in type V neuropathy. Conclusions: FSR facilitates tumor control, either as an initial treatment option or in combination with microsurgery. In addition to being a safe procedure with few side effects, FSR offers the significant benefit of superior functional outcomes.« less

Colony formation by normal and malignant human B-lymphocytes.

PubMed Central

Izaguirre, C. A.; Minden, M. D.; Howatson, A. F.; McCulloch, E. A.

1980-01-01

A method is described that permits colony formation in culture by B lymphocytes from normal blood and from blood, marrow or lymph nodes of patients with myeloma or lymphoma. The method depends on: (1) exhaustively depleting cell suspensions of T lymphocytes, (2) a medium conditioned by T lymphocytes in the presence of phytohaemagglutinin (PHA-TCM), and (3) irradiated autologous or homologous T lymphocytes. Under these conditions the assay is linear. Cellular development of B lymphocytes can be followed; differentiation to plasma cells is seen in cultures of cells from normal individuals and myeloma patients, but not lymphoma patients. Malignant B lymphocytes in culture produced immunoglobulin of the class identified in the patient's blood, or in freshly obtained cells. We conclude that the assay is suitable for studying the growth, differentiation and regulation of normal and malignant B lymphocytes in culture. Images Fig. 1 Fig. 2 PMID:6968572

Iterative local Gaussian clustering for expressed genes identification linked to malignancy of human colorectal carcinoma.

PubMed

Wasito, Ito; Hashim, Siti Zaiton M; Sukmaningrum, Sri

2007-12-30

Gene expression profiling plays an important role in the identification of biological and clinical properties of human solid tumors such as colorectal carcinoma. Profiling is required to reveal underlying molecular features for diagnostic and therapeutic purposes. A non-parametric density-estimation-based approach called iterative local Gaussian clustering (ILGC), was used to identify clusters of expressed genes. We used experimental data from a previous study by Muro and others consisting of 1,536 genes in 100 colorectal cancer and 11 normal tissues. In this dataset, the ILGC finds three clusters, two large and one small gene clusters, similar to their results which used Gaussian mixture clustering. The correlation of each cluster of genes and clinical properties of malignancy of human colorectal cancer was analysed for the existence of tumor or normal, the existence of distant metastasis and the existence of lymph node metastasis.

p16(INK4a) -mediated suppression of telomerase in normal and malignant human breast cells.

PubMed

Bazarov, Alexey V; Van Sluis, Marjolein; Hines, William C; Bassett, Ekaterina; Beliveau, Alain; Campeau, Eric; Mukhopadhyay, Rituparna; Lee, Won Jae; Melodyev, Sonya; Zaslavsky, Yuri; Lee, Leonard; Rodier, Francis; Chicas, Agustin; Lowe, Scott W; Benhattar, Jean; Ren, Bing; Campisi, Judith; Yaswen, Paul

2010-10-01

The cyclin-dependent kinase inhibitor p16(INK4a) (CDKN2A) is an important tumor suppressor gene frequently inactivated in human tumors. p16 suppresses the development of cancer by triggering an irreversible arrest of cell proliferation termed cellular senescence. Here, we describe another anti-oncogenic function of p16 in addition to its ability to halt cell cycle progression. We show that transient expression of p16 stably represses the hTERT gene, encoding the catalytic subunit of telomerase, in both normal and malignant breast epithelial cells. Short-term p16 expression increases the amount of histone H3 trimethylated on lysine 27 (H3K27) bound to the hTERT promoter, resulting in transcriptional silencing, likely mediated by polycomb complexes. Our results indicate that transient p16 exposure may prevent malignant progression in dividing cells by irreversible repression of genes, such as hTERT, whose activity is necessary for extensive self-renewal. © 2010 The Authors Aging Cell © 2010 Blackwell Publishing Ltd/Anatomical Society of Great Britain and Ireland.

Pre-malignant lymphoid cells arise from hematopoietic stem/progenitor cells in chronic lymphocytic leukemia.

PubMed

Kikushige, Yoshikane; Miyamoto, Toshihiro

2015-11-01

Human malignancies progress through a multistep process that includes the development of critical somatic mutations over the clinical course. Recent novel findings have indicated that hematopoietic stem cells (HSCs), which have the potential to self-renew and differentiate into multilineage hematopoietic cells, are an important cellular target for the accumulation of critical somatic mutations in hematological malignancies and play a central role in myeloid malignancy development. In contrast to myeloid malignancies, mature lymphoid malignancies, such as chronic lymphocytic leukemia (CLL), are thought to originate directly from differentiated mature lymphocytes; however, recent compelling data have shown that primitive HSCs and hematopoietic progenitor cells contribute to the pathogenesis of mature lymphoid malignancies. Several representative mutations of hematological malignancies have been identified within the HSCs of CLL and lymphoma patients, indicating that the self-renewing long-lived fraction of HSCs can serve as a reservoir for the development of oncogenic events. Novel mice models have been established as human mature lymphoma models, in which specific oncogenic events target the HSCs and immature progenitor cells. These data collectively suggest that HSCs can be the cellular target involved in the accumulation of oncogenic events in the pathogenesis of mature lymphoid and myeloid malignancies.

Malignant hyperthermia

MedlinePlus

... about MH: Malignant Hyperthermia Association of the United States -- www.mhaus.org National Organization for Rare Disorders -- rarediseases.org/rare-diseases/malignant-hyperthermia NIH Genetics Home Reference -- ghr.nlm.nih.gov/condition/malignant-hyperthermia

Occipital Neuralgia as the Only Presenting Symptom of Foramen Magnum Meningioma

PubMed Central

Yang, Seung-Yeob; Koo, Joon-Bum; Jeong, Sang-Wuk

2009-01-01

Background Occipital neuralgia (ON) is a condition characterized by a paroxysmal stabbing pain in the area of the greater or lesser occipital nerves; it is usually regarded by clinicians as idiopathic. Some have suggested that ON can be induced by trauma or injury of the occipital nerves or their roots, but tumor has rarely been reported as a cause of ON. Case Report We report herein a case of foramen magnum meningioma in a 55-year-old woman who presented with ON triggered by head motion as the only symptom without any signs of myelopathy. Conclusions This case indicates that it is important to consider the underlying causes of ON. Precise neurologic and radiological evaluations such as cervical spine magnetic resonance imaging are needed. PMID:20076803

Tumor malignancy is engaged to prokaryotic homolog toolbox.

PubMed

Fernandes, Janaina; Guedes, Patrícia G; Lage, Celso Luiz S; Rodrigues, Juliany Cola F; Lage, Claudia de Alencar S

2012-04-01

Cancer cells display high proliferation rates and survival provided by high glycolysis, chemoresistance and radioresistance, metabolic features that appear to be activated with malignancy, and seemed to have arisen as early in evolution as in unicellular/prokaryotic organisms. Based on these assumptions, we hypothesize that aggressive phenotypes found in malignant cells may be related to acquired unicellular behavior, launched within a tumor when viral and prokaryotic homologs are overexpressed performing likely robust functions. The ensemble of these expressed viral and prokaryotic close homologs in the proteome of a tumor tissue gives them advantage over normal cells. To assess the hypothesis validity, sequences of human proteins involved in apoptosis, energetic metabolism, cell mobility and adhesion, chemo- and radio-resistance were aligned to homologs present in other life forms, excluding all eukaryotes, using PSI-BLAST, with further corroboration from data available in the literature. The analysis revealed that selected sequences of proteins involved in apoptosis and tumor suppression (as p53 and pRB) scored non-significant (E-value>0.001) with prokaryotic homologs; on the other hand, human proteins involved in cellular chemo- and radio-resistance scored highly significant with prokaryotic and viral homologs (as catalase, E-value=zero). We inferred that such upregulated and/or functionally activated proteins in aggressive malignant cells represent a toolbox of modern human homologs evolved from a similar key set that have granted survival of ancient prokaryotes against extremely harsh environments. According to what has been discussed along this analysis, high mutation rates usually hit hotspots in important conserved protein domains, allowing uncontrolled expansion of more resistant, death-evading malignant clones. That is the case of point mutations in key viral proteins affording viruses escape to chemotherapy, and human homologs of such retroviral

Enhanced Anti-Tumor Effect of Zoledronic Acid Combined with Temozolomide against Human Malignant Glioma Cell Expressing O6-Methylguanine DNA Methyltransferase

PubMed Central

Fukai, Junya; Koizumi, Fumiaki; Nakao, Naoyuki

2014-01-01

Temozolomide (TMZ), a DNA methylating agent, is widely used in the adjuvant treatment of malignant gliomas. O6-methylguanine-DNA methyltranferase (MGMT), a DNA repair enzyme, is frequently discussed as the main factor that limits the efficacy of TMZ. Zoledronic acid (ZOL), which is clinically applied to treat cancer-induced bone diseases, appears to possess direct anti-tumor activity through apoptosis induction by inhibiting mevalonate pathway and prenylation of intracellular small G proteins. In this study, we evaluated whether ZOL can be effectively used as an adjuvant to TMZ in human malignant glioma cells that express MGMT. Malignant glioma cell lines, in which the expression of MGMT was detected, did not exhibit growth inhibition by TMZ even at a longer exposure. However, combination experiment of TMZ plus ZOL revealed that a supra-additive effect resulted in a significant decrease in cell growth. In combined TMZ/ZOL treatment, an increased apoptotic rate was apparent and significant activation of caspase-3 and cleavage of poly-(ADP-ribose) polymerase were observed compared with each single drug exposure. There were decreased amounts of Ras-GTP, MAPK and Akt phosphorylation and MGMT expression in the ZOL-treated cells. Subcutanous xenograft models showed significant decrease of tumor growth with combined TMZ/ZOL treatment. These results suggest that ZOL efficaciously inhibits activity of Ras in malignant glioma cells and potentiates TMZ-mediated cytotoxicity, inducing growth inhibition and apoptosis of malignant glioma cells that express MGMT and resistant to TMZ. Based on this work, combination of TMZ with ZOL might be a potential therapy in malignant gliomas that receive less therapeutic effects of TMZ due to cell resistance. PMID:25111384

Melanocytoma-like melanoma may be the missing link between benign and malignant uveal melanocytic lesions in humans and dogs: a comparative study.

PubMed

Zoroquiain, Pablo; Mayo-Goldberg, Erin; Alghamdi, Sarah; Alhumaid, Sulaiman; Perlmann, Eduardo; Barros, Paulo; Mayo, Nancy; Burnier, Miguel N

2016-12-01

The cutoff presented in the current classification of canine melanocytic lesions by Wilcock and Pfeiffer is based on the clinical outcome rather than morphological concepts. Classification of tumors based on morphology or molecular signatures is the key to identifying new therapies or prognostic factors. Therefore, the aim of this study was to analyze morphological findings in canine melanocytic lesions based on classic malignant morphologic principles of neoplasia and to compare these features with human uveal melanoma (HUM) samples. In total, 64 canine and 111 human morphologically malignant melanocytic lesions were classified into two groups (melanocytoma-like or classic melanoma) based on the presence or absence of M cells, respectively. Histopathological characteristics were compared between the two groups using the χ-test, t-test, and multivariate discriminant analysis. Among the 64 canine tumors, 28 (43.7%) were classic and 36 (56.3%) were melanocytoma-like melanomas. Smaller tumor size, a higher degree of pigmentation, and lower mitotic activity distinguished melanocytoma-like from classic tumors with an accuracy of 100% for melanocytoma-like lesions. From the human series, only one case showed melanocytoma-like features and had a low risk for metastasis characteristics. Canine uveal melanoma showed a morphological spectrum with features similar to the HUM counterpart (classic melanoma) and overlapped features between uveal melanoma and melanocytoma (melanocytoma-like melanoma). Recognition that the subgroup of melanocytoma-like melanoma may represent the missing link between benign and malignant lesions could help explain the progression of uveal melanoma in dogs; these findings can potentially be translated to HUM.

Microdeletion del(22)(q12.2) encompassing the facial development-associated gene, MN1 (meningioma 1) in a child with Pierre-Robin sequence (including cleft palate) and neurofibromatosis 2 (NF2): a case report and review of the literature.

PubMed

Davidson, Tom B; Sanchez-Lara, Pedro A; Randolph, Linda M; Krieger, Mark D; Wu, Shi-Qi; Panigrahy, Ashok; Shimada, Hiroyuki; Erdreich-Epstein, Anat

2012-03-22

Pierre-Robin sequence (PRS) is defined by micro- and/or retrognathia, glossoptosis and cleft soft palate, either caused by deformational defect or part of a malformation syndrome. Neurofibromatosis type 2 (NF2) is an autosomal dominant syndrome caused by mutations in the NF2 gene on chromosome 22q12.2. NF2 is characterized by bilateral vestibular schwannomas, spinal cord schwannomas, meningiomas and ependymomas, and juvenile cataracts. To date, NF2 and PRS have not been described together in the same patient. We report a female with PRS (micrognathia, cleft palate), microcephaly, ocular hypertelorism, mental retardation and bilateral hearing loss, who at age 15 was also diagnosed with severe NF2 (bilateral cerebellopontine schwannomas and multiple extramedullary/intradural spine tumors). This is the first published report of an individual with both diagnosed PRS and NF2. High resolution karyotype revealed 46, XX, del(22)(q12.1q12.3), FISH confirmed a deletion encompassing NF2, and chromosomal microarray identified a 3,693 kb deletion encompassing multiple genes including NF2 and MN1 (meningioma 1).Five additional patients with craniofacial dysmorphism and deletion in chromosome 22-adjacent-to or containing NF2 were identified in PubMed and the DECIPHER clinical chromosomal database. Their shared chromosomal deletion encompassed MN1, PITPNB and TTC28. MN1, initially cloned from a patient with meningioma, is an oncogene in murine hematopoiesis and participates as a fusion gene (TEL/MN1) in human myeloid leukemias. Interestingly, Mn1-haploinsufficient mice have abnormal skull development and secondary cleft palate. Additionally, Mn1 regulates maturation and function of calvarial osteoblasts and is an upstream regulator of Tbx22, a gene associated with murine and human cleft palate. This suggests that deletion of MN1 in the six patients we describe may be causally linked to their cleft palates and/or craniofacial abnormalities. Thus, our report describes a NF2-adjacent

Molecular-Guided Therapy for Childhood Cancer

ClinicalTrials.gov

2017-07-07

Neuroblastoma; Medulloblastoma; Glioma; Ependymoma; Choroid Plexus Neoplasms; Craniopharyngioma; Dysembryoplastic Neuroepithelial Tumor; Meningioma; Primitive Neuroectodermal Tumors (PNETs); Germ Cell Tumors; Rhabdomyosarcoma; Non-rhabdomyosarcoma; Ewings Sarcoma; Osteosarcoma; Wilms Tumor; Renal Cell Carcinoma; Malignant Rhabdoid Tumor; Clear Cell Sarcoma; Liver Tumors

Vibrational Profiling of Brain Tumors and Cells

PubMed Central

Nelson, Sultan L; Proctor, Dustin T; Ghasemloonia, Ahmad; Lama, Sanju; Zareinia, Kourosh; Ahn, Younghee; Al-Saiedy, Mustafa R; Green, Francis HY; Amrein, Matthias W; Sutherland, Garnette R

2017-01-01

This study reports vibration profiles of neuronal cells and tissues as well as brain tumor and neocortical specimens. A contact-free method and analysis protocol was designed to convert an atomic force microscope into an ultra-sensitive microphone with capacity to record and listen to live biological samples. A frequency of 3.4 Hz was observed for both cultured rat hippocampal neurons and tissues and vibration could be modulated pharmacologically. Malignant astrocytoma tissue samples obtained from operating room, transported in artificial cerebrospinal fluid, and tested within an hour, vibrated with a much different frequency profile and amplitude, compared to meningioma or lateral temporal cortex providing a quantifiable measurement to accurately distinguish the three tissues in real-time. Vibration signals were converted to audible sound waves by frequency modulation, thus demonstrating, acoustic patterns unique to meningioma, malignant astrocytoma and neocortex. PMID:28744324

FT-IR Spectroscopic Analysis of Normal and Malignant Human Oral Tissues

NASA Astrophysics Data System (ADS)

Krishnakumar, N.; Madhavan, R. Nirmal; Sumesh, P.; Palaniappan, Pl. Rm.; Venkatachalam, P.; Ramachandran, C. R.

2008-11-01

FT-IR spectroscopy has been used to explore the changes in the vibrational bands of normal and oral squamous cell carcinoma (OSCC) tissues in the region 4000-400 cm-1. Significant changes in the spectral features were observed. The spectral changes were the results of characteristics structural alterations at the molecular level in the malignant tissues. These alterations include structural changes of proteins and possible increase of its content, an increase in the nucleic-to-cytoplasm ratio, an increase in the relative amount of DNA, an increase in the rate of phosphorylation process induced by carcinogenesis, a loss of hydrogen bonding of the C-OH groups in the amino acid residues of proteins, a decrease in the relative amount of lipids compared to normal epithelial oral tissues. The results of the present study demonstrate that the FT-IR technique has the feasibility of discriminating malignant from normal tissues and other pathological states in a short period of time and may detect malignant transformation earlier than the standard histological examination stage.

Risk of Recurrence in Operated Parasagittal Meningiomas: A Logistic Binary Regression Model.

PubMed

Escribano Mesa, José Alberto; Alonso Morillejo, Enrique; Parrón Carreño, Tesifón; Huete Allut, Antonio; Narro Donate, José María; Méndez Román, Paddy; Contreras Jiménez, Ascensión; Pedrero García, Francisco; Masegosa González, José

2018-02-01

Parasagittal meningiomas arise from the arachnoid cells of the angle formed between the superior sagittal sinus (SSS) and the brain convexity. In this retrospective study, we focused on factors that predict early recurrence and recurrence times. We reviewed 125 patients with parasagittal meningiomas operated from 1985 to 2014. We studied the following variables: age, sex, location, laterality, histology, surgeons, invasion of the SSS, Simpson removal grade, follow-up time, angiography, embolization, radiotherapy, recurrence and recurrence time, reoperation, neurologic deficit, degree of dependency, and patient status at the end of follow-up. Patients ranged in age from 26 to 81 years (mean 57.86 years; median 60 years). There were 44 men (35.2%) and 81 women (64.8%). There were 57 patients with neurologic deficits (45.2%). The most common presenting symptom was motor deficit. World Health Organization grade I tumors were identified in 104 patients (84.6%), and the majority were the meningothelial type. Recurrence was detected in 34 cases. Time of recurrence was 9 to 336 months (mean: 84.4 months; median: 79.5 months). Male sex was identified as an independent risk for recurrence with relative risk 2.7 (95% confidence interval 1.21-6.15), P = 0.014. Kaplan-Meier curves for recurrence had statistically significant differences depending on sex, age, histologic type, and World Health Organization histologic grade. A binary logistic regression was made with the Hosmer-Lemeshow test with P > 0.05; sex, tumor size, and histologic type were used in this model. Male sex is an independent risk factor for recurrence that, associated with other factors such tumor size and histologic type, explains 74.5% of all cases in a binary regression model. Copyright © 2017 Elsevier Inc. All rights reserved.

Global Variation of Human Papillomavirus Genotypes and Selected Genes Involved in Cervical Malignancies.

PubMed

Husain, R S Akram; Ramakrishnan, V

2015-01-01

Carcinoma of the cervix is ranked second among the top 5 cancers affecting women globally. Parallel to other cancers, it is also a complex disease involving numerous factors such as human papillomavirus (HPV) infection followed by the activity of oncogenes and environmental factors. The incidence rate of the disease remains high in developing countries due to lack of awareness, followed by mass screening programs, various socioeconomic issues, and low usage of preventive vaccines. Over the past 3 decades, extensive research has taken place in cervical malignancy to elucidate the role of host genes in the pathogenesis of the disease, yet it remains one of the most prevalent diseases. It is imperative that recent genome-wide techniques be used to determine whether carcinogenesis of oncogenes is associated with cervical cancer at the molecular level and to translate that knowledge into developing diagnostic and therapeutic tools. The aim of this study was to discuss HPV predominance with their genotype distribution worldwide, and in India, as well as to discuss the newly identified oncogenes related to cervical cancer in current scenario. Using data from various databases and robust technologies, oncogenes associated with cervical malignancies were identified and are explained in concise manner. Due to the advent of recent technologies, new candidate genes are explored and can be used as precise biomarkers for screening and developing drug targets. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Expression of metalloprotease insulin-degrading enzyme (insulysin) in normal and malignant human tissues

PubMed Central

Yfanti, Christina; Mengele, Karin; Gkazepis, Apostolos; Weirich, Gregor; Giersig, Cecylia; Kuo, Wen-Liang; Tang, Wei-Jen; Rosner, Marsha; Schmitt, Manfred

2013-01-01

Background Insulin-degrading enzyme (IDE, insulysin, insulinase; EC 3.4.22.11), a thiol metalloendopeptidase, is involved in intracellular degradation of insulin, thereby inhibiting its translocation and accumulation to the nucleus. Recently, protein expression of IDE has been demonstrated in the epithelial ducts of normal breast and in breast cancer tissue (Radulescu et al., Int J Oncol 30:73; 2007). Materials and Methods Utilizing four different antibodies generated against different epitopes of the IDE molecule, we performed western blot analysis and immunohistochemical staining on several normal human tissues, on a plethora of tumor cell lines of different tissue origin, and on malignant breast and ovarian tissue. Results Applying the four IDE-directed antibodies, we demonstrate IDE expression at the protein level, both by means of immunoblotting and immunocytochemistry, in all of the tumor cell lines analyzed. Besides, IDE protein expression was found in normal tissues of the kidney, liver, lung, brain, breast and skeletal muscle, as well as in breast and ovarian cancer tissues. Immunohistochemical visualization of IDE indicated cytoplasmic localization of IDE in all of the cell lines and tissues assessed. Conclusions We performed for the first time a wide-ranging survey on IDE protein expression in normal and malignant tissues and cells and thus extend knowledge about cellular and tissue distribution of IDE, an enzyme which so far has mainly been studied in connection with Alzheimer’s disease and diabetes but not in cancer. PMID:18813847

Primary Intracranial Myoepithelial Neoplasm: A Potential Mimic of Meningioma.

PubMed

Choy, Bonnie; Pytel, Peter

2016-05-01

Myoepithelial neoplasms were originally described in the salivary glands but their spectrum has been expanding with reports in other locations, including soft tissue. Intracranial cases are exceptionally rare outside the sellar region where they are assumed to be arising from Rathke pouch rests. Two cases of pediatric intracranial myoepithelial neoplasm in the interhemispheric fissure and the right cerebral hemisphere are reported here. Imaging studies suggest that the second case was associated with cerebrospinal fluid dissemination. Both cases showed typical variation in morphology and immunophenotype between more epithelioid and more mesenchymal features. The differential diagnosis at this particular anatomic location includes meningioma, which can show some overlap in immunophenotype since both tumors express EMA as well as GLUT1. One case was positive for EWSR1 rearrangement by fluorescence in situ hybridization. One patient is disease free at last follow-up while the other succumbed to the disease within days illustrating the clinical spectrum of these tumors. © The Author(s) 2015.

Early and late postoperative seizure outcome in 97 patients with supratentorial meningioma and preoperative seizures: a retrospective study.

PubMed

Zheng, Zhe; Chen, Peng; Fu, Weiming; Zhu, Junming; Zhang, Hong; Shi, Jian; Zhang, Jianmin

2013-08-01

We identified factors associated with early and late postoperative seizure control in patients with supratentorial meningioma plus preoperative seizures. In this retrospective study, univariate analysis and multivariate logistic regression analysis compared 24 clinical variables according to the occurrence of early (≤1 week) or late (>1 week) postoperative seizures. Sixty-two of 97 patients (63.9 %) were seizure free for the entire postoperative follow-up period (29.5 ± 11.8 months), while 13 patients (13.4 %) still had frequent seizures at the end of follow-up. Fourteen of 97 patients (14.4 %) experienced early postoperative seizures, and emergence of new postoperative neurological deficits was the only significant risk factor (odds ratio = 7.377). Thirty-three patients (34.0 %) experienced late postoperative seizures at some time during follow-up, including 12 of 14 patients with early postoperative seizures. Associated risk factors for late postoperative seizures included tumor progression (odds ratio = 7.012) and new permanent postoperative neurological deficits (odds ratio = 4.327). Occurrence of postoperative seizures in patients with supratentorial meningioma and preoperative seizure was associated with new postoperative neurological deficits. Reduced cerebral or vascular injury during surgery may lead to fewer postoperative neurological deficits and better seizure outcome.

Toxicological characterization of ZnO nanoparticles in malignant and non-malignant cells.

PubMed

Moratin, Helena; Scherzad, Agmal; Gehrke, Thomas; Ickrath, Pascal; Radeloff, Katrin; Kleinsasser, Norbert; Hackenberg, Stephan

2018-04-01

The increasing usage of zinc oxide nanoparticles (ZnO-NPs) in industrial applications as well as in consumer products raises concern regarding their potential adverse effects to a greater extend. Numerous studies have demonstrated toxic properties of NPs, however there is still a lack of knowledge concerning the underlying mechanisms. This study was designed to systematically investigate cytotoxicity, apoptosis, cell cycle alterations, and genotoxicity induced by ZnO-NP. Moreover, it was an aim of the investigations to specify the diverse effects of nanoparticle exposure in malignant in comparison with non-malignant cells. Therefore, human head and neck squamous cell carcinoma-derived FaDu cells were incubated with 4-20 µg/ml of ZnO-NPs for 1-48 hr and tested for cell viability, cell cycle alterations, apoptosis and caspase-3 gene expression as a sensitive marker of molecular apoptotic processes with regard to time- and dose-dependent effects. Human mesenchymal bone marrow stem cells were used as non-malignant representatives to examine oxidative stress-related genotoxicity. Results showed a significant reduction in cell viability as well as dose- and time-dependent increase of apoptotic cells following nanoparticle treatment. Likewise, caspase-3 gene expression enhanced already before first apoptotic cells were detectable. It could be observed that doses that were cytotoxic in tumor cells did not reduce viability in stem cells. However, the same concentrations already induced significant DNA damage. The findings of the study suggest to keep a more critical eye on the use of nanoparticles as anti-cancer agents. Yet, additional in vivo studies are needed to assess safety concerns for consumers and patients. Environ. Mol. Mutagen. 59:247-259, 2018. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Iterative local Gaussian clustering for expressed genes identification linked to malignancy of human colorectal carcinoma

PubMed Central

Wasito, Ito; Hashim, Siti Zaiton M; Sukmaningrum, Sri

2007-01-01

Gene expression profiling plays an important role in the identification of biological and clinical properties of human solid tumors such as colorectal carcinoma. Profiling is required to reveal underlying molecular features for diagnostic and therapeutic purposes. A non-parametric density-estimation-based approach called iterative local Gaussian clustering (ILGC), was used to identify clusters of expressed genes. We used experimental data from a previous study by Muro and others consisting of 1,536 genes in 100 colorectal cancer and 11 normal tissues. In this dataset, the ILGC finds three clusters, two large and one small gene clusters, similar to their results which used Gaussian mixture clustering. The correlation of each cluster of genes and clinical properties of malignancy of human colorectal cancer was analysed for the existence of tumor or normal, the existence of distant metastasis and the existence of lymph node metastasis. PMID:18305825

Dielectric properties of human normal, malignant and cirrhotic liver tissue: in vivo and ex vivo measurements from 0.5 to 20 GHz using a precision open-ended coaxial probe.

PubMed

O'Rourke, Ann P; Lazebnik, Mariya; Bertram, John M; Converse, Mark C; Hagness, Susan C; Webster, John G; Mahvi, David M

2007-08-07

Hepatic malignancies have historically been treated with surgical resection. Due to the shortcomings of this technique, there is interest in other, less invasive, treatment modalities, such as microwave hepatic ablation. Crucial to the development of this technique is the accurate knowledge of the dielectric properties of human liver tissue at microwave frequencies. To this end, we characterized the dielectric properties of in vivo and ex vivo normal, malignant and cirrhotic human liver tissues from 0.5 to 20 GHz. Analysis of our data at 915 MHz and 2.45 GHz indicates that the dielectric properties of ex vivo malignant liver tissue are 19 to 30% higher than normal tissue. The differences in the dielectric properties of in vivo malignant and normal liver tissue are not statistically significant (with the exception of effective conductivity at 915 MHz, where malignant tissue properties are 16% higher than normal). Also, the dielectric properties of in vivo normal liver tissue at 915 MHz and 2.45 GHz are 16 to 43% higher than ex vivo. No statistically significant differences were found between the dielectric properties of in vivo and ex vivo malignant tissue (with the exception of effective conductivity at 915 MHz, where malignant tissue properties are 28% higher than normal). We report the one-pole Cole-Cole parameters for ex vivo normal, malignant and cirrhotic liver tissue in this frequency range. We observe that wideband dielectric properties of in vivo liver tissue are different from the wideband dielectric properties of ex vivo liver tissue, and that the in vivo data cannot be represented in terms of a Cole-Cole model. Further work is needed to uncover the mechanisms responsible for the observed wideband trends in the in vivo liver data.

A syngeneic glioma model to assess the impact of neural progenitor target cell age on tumor malignancy

PubMed Central

Mikheev, Andrei M; Stoll, Elizabeth A; Mikheeva, Svetlana A; Maxwell, John-Patrick; Jankowski, Pawel P; Ray, Sutapa; Uo, Takuma; Morrison, Richard S; Horner, Philip J; Rostomily, Robert C

2010-01-01

Summary Human glioma incidence, malignancy and treatment resistance are directly proportional to patient age. Cell intrinsic factors are reported to contribute to human age-dependent glioma malignancy but suitable animal models to examine the role of aging are lacking. Here we developed an orthotopic syngeneic glioma model to test the hypothesis that the age of neural progenitor cells (NPCs), presumed cells of glioma origin, influences glioma malignancy. Gliomas generated from transformed donor 3-, 12-, and 18-month-old NPCs in same-aged adult hosts all formed highly invasive glial tumors that phenocopied the human disease. Survival analysis indicated increased malignancy of gliomas generated from older 12- and 18-month-old transformed NPCs compared with their 3-month counterparts (median survival of 38.5 and 42.5 vs. 77 days, respectively). This study showed for the first time that age of target cells at the time of transformation can affect malignancy and demonstrated the feasibility of a syngeneic model using transformed NPCs for future examination of the relative impacts of age-related cell intrinsic and cell-extrinsic factors in glioma malignancy. PMID:19489742

Asbestos-related malignancy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Talcott, J.A.; Antman, K.H.

Asbestos-associated malignancies have received significant attention in the lay and medical literature because of the increasing frequency of two asbestos-associated tumors, lung carcinoma and mesothelioma; the wide distribution of asbestos; its status as a prototype environmental carcinogen; and the many recent legal compensation proceedings, for which medical testimony has been required. The understanding of asbestos-associated carcinogenesis has increased through study of animal models, human epidemiology, and, recently, the application of modern molecular biological techniques. However, the detailed mechanisms of carcinogenesis remain unknown. A wide variety of malignancies have been associated with asbestos, although the strongest evidence for a causal associationmore » is confined to lung cancer and mesothelioma. Epidemiological studies have provided evidence that both the type of asbestos fiber and the industry in which the exposure occurs may affect the rates of asbestos-associated cancers. It has been shown that asbestos exerts a carcinogenic effect independent of exposure to cigarette smoking that, for lung cancers, is synergistically enhanced by smoking. Other questions remain controversial, such as whether pulmonary fibrosis necessarily precedes asbestos-associated lung cancer and whether some threshold level of exposure to asbestos (including low-dose exposures that may occur in asbestos-associated public buildings) may be safe. Mesothelioma, the most closely asbestos-associated malignancy, has a dismal natural history and has been highly resistant to therapy. However, investigational multi-modality therapy may offer benefit to some patients. 179 references.« less

Targeting the Interleukin-6/Jak/Stat Pathway in Human Malignancies

PubMed Central

Sansone, Pasquale; Bromberg, Jacqueline

2012-01-01

The Janus kinase/signal transducer and activator of transcription (Jak/Stat) pathway was discovered 20 years ago as a mediator of cytokine signaling. Since this time, more than 2,500 articles have been published demonstrating the importance of this pathway in virtually all malignancies. Although there are dozens of cytokines and cytokine receptors, four Jaks, and seven Stats, it seems that interleukin-6–mediated activation of Stat3 is a principal pathway implicated in promoting tumorigenesis. This transcription factor regulates the expression of numerous critical mediators of tumor formation and metastatic progression. This review will examine the relative importance and function of this pathway in nonmalignant conditions as well as malignancies (including tumor intrinsic and extrinsic), the influence of other Stats, the development of inhibitors to this pathway, and the potential role of inhibitors in controlling or eradicating cancers. PMID:22355058

Temporal trends in treatment and subsequent neoplasm risk among five-year survivors of childhood cancer, 1970-2015

PubMed Central

Turcotte, Lucie M.; Liu, Qi; Yasui, Yutaka; Arnold, Michael A.; Hammond, Sue; Howell, Rebecca M.; Smith, Susan A.; Weathers, Rita E.; Henderson, Tara O.; Gibson, Todd M.; Leisenring, Wendy; Armstrong, Gregory T.; Robison, Leslie L; Neglia, Joseph P.

2017-01-01

Importance Cancer treatments are associated with subsequent neoplasms in childhood cancer survivors. It is unknown whether temporal changes in therapy are associated with changes in subsequent neoplasm risk. Objective Quantify the association between temporal treatment dosing changes and subsequent neoplasm risk. Design, Setting, Participants Retrospective, multicenter cohort of five-year cancer survivors diagnosed before age 21 years from pediatric tertiary hospitals in the United States and Canada between 1970-1999, with follow-up through December 2015. Exposures Radiation and chemotherapy dose changes over time. Main Outcomes and Measures Subsequent neoplasm 15-year cumulative incidence, cumulative burden, and standardized incidence ratios (SIRs) for subsequent malignancies were compared by treatment decade. Multivariable models assessed relative rates (RRs) of subsequent neoplasms by 5-year increments, adjusting for demographic and clinical characteristics. Mediation analyses assessed whether changes in subsequent neoplasm rates over time were mediated by treatment variable modifications. Results Among 23,603 childhood cancer survivors (mean age at diagnosis, 7.7 years; 46% female) the most common initial diagnoses were acute lymphoblastic leukemia, Hodgkin lymphoma and astrocytoma. During a mean follow up of 20.5 years (374,638 person-years at risk), 1,639 survivors experienced 3,115 subsequent neoplasms, including 1,026 malignancies, 233 benign meningiomas, and 1,856 non-melanoma skin cancers. The most common subsequent malignancies were breast and thyroid cancers. Individuals receiving radiation decreased (1970s, 77% vs. 1990s, 33%), as did median dose (1970s, 30 Gy [IQR 24-44] vs. 1990s, 26 Gy [IQR 18-45]). Fifteen-year cumulative incidence of subsequent malignancies decreased by decade of diagnosis (1990s: 1.3%, 95%CI 1.1-1.5, 1980s: 1.7%, 95%CI 1.5-2.0, 1970s: 2.1%, 95%CI 1.7-2.4). Reference absolute rates per 1,000 person-years for subsequent

Oral malignant melanomas and other head and neck neoplasms in Danish dogs - data from the Danish Veterinary Cancer Registry

PubMed Central

2009-01-01

Background Head and neck cancers (HNC) are relatively common and often very serious diseases in both dogs and humans. Neoplasms originating in the head and neck region are a heterogeneous group. HNC often has an unfavourable prognosis and the proximity of the tissue structures renders extirpation of tumours with sufficient margins almost incompatible with preservation of functionality. In humans oral malignant melanoma (OMM) is extremely rare, but represents a particular challenge since it is highly aggressive as is the canine counterpart, which thus may be of interest as a spontaneous animal model. Methods Canine cases entered in the Danish Veterinary Cancer Registry (DVCR) from May 15th 2005 through February 29th 2008 were included in this study. Fisher's exact test was used to compare proportions of HNC in dogs and humans as well as proportions of surgically treated cases of OMM and squamous cell carcinomas (SCC). Also the proportions of benign and malignant neoplasms of different locations in dogs were compared using Fisher's exact test. Results A total of 1768 cases of neoplasias (679 malignant, 826 benign, 263 unknown) were submitted. Of all neoplasias HNC accounted for 7.2% (n = 128). Of these, 64 (50%) were malignant and 44 (34%) benign. The most common types of malignant neoplasia were SCC (18; 28% of malignant), OMM (13; 20% of malignant), soft tissue sarcoma (11; 17% of malignant) and adenocarcinoma (5; 11% of malignant). The most common types of benign neoplasms were adenoma (7; 16% of benign), polyps (6; 14% of benign) and fibroma (5; 11% of benign). Conclusions In the current study, the proportion of neoplasia in the head and neck region in dogs in Denmark was similar to other canine studies and significantly more common than in humans with a large proportion of malignancies. Spontaneous HNC in dogs thus, may serve as a model for HNC in humans. Canine OMM is a spontaneous cancer in an outbred, immune-competent large mammal population and could be a

Role of human papillomavirus in oral squamous cell carcinoma and oral potentially malignant disorders: A review of the literature

PubMed Central

Gupta, Shikha; Gupta, Sunita

2015-01-01

Human papillomaviruses (HPVs) are epitheliotropic viruses with an affinity for keratinocytes and are principally found in the anogenital tract, urethra, skin, larynx, tracheobronchial and oral mucosa. On the basis of high, but variable frequency of HPV in oral squamous cell carcinoma (OSCC), malignant potential of HPV infection has been hypothesized but not definitely confirmed. The aim of this review was to highlight the genomic structure and possible mechanism of infection and carcinogenesis by HPV in the oral mucosa and to review the frequency of HPV prevalence in OSCC and oral potentially malignant disorders. A computer database search was performed through the use of PubMed from 1994 to 2014. Search keywords used were: HPV and oral cancer, HPV and oral leukoplakia, HPV and oral lichen planus, HPV and OSCC, HPV and verrucous carcinoma, HPV and proliferative verrucous leukoplakia, HPV and oral papilloma. PMID:26097339

Anterolateral meningioma of the foramen magnum and high cervical spine presenting intradural and extradural growth in a child: case report and literature review.

PubMed

Athanasiou, Alkinoos; Magras, Ioannis; Sarlis, Panagiotis; Spyridopoulos, Evangelos; Polyzoidis, Konstantinos

2015-12-01

We report a rare case of anterolateral meningioma of the foramen magnum (FMM) and high cervical spine presenting both intradural and extradural growth in a 7.5-year-old boy. We also performed a review of the relevant peer-reviewed literature. The patient presented with progressive tetraparesis and gait instability. Neuroimaging revealed an anterolateral tumor of the foramen magnum, C1 and C2 cervical spine level. The patient was treated in two stages: During the first operation, the extradural part was resected while the intradural part was removed in a second operation. Following the second operation, the patient showed almost complete neurological recovery as a result of cervical spinal cord and brainstem decompression but was complicated with cerebrospinal fluid leakage and infection by Acinetobacter. He sustained two further operations for dural sealing and external ventricular drainage and was treated with intraventricular administration of antibiotics. Histopathology of the tumor confirmed a meningotheliomatous meningioma. At the 6-month post-op follow-up examination, the patient exhibited complete neurological recovery and no radiological tumor recurrence. To the authors' best knowledge, we report the third case of sporadic pediatric meningioma of the foramen magnum and high cervical compartments with an extradural growth. Accurate pre-operative estimation of possible extradural growth is crucial towards surgical planning and sufficient treatment. Treatment of choice is total resection in a single operating session to avoid re-operations and increased risk of complications. If not possible, a re-operation should always attempt to secure the desired result.

Familial association of specific histologic types of ovarian malignancy with other malignancies.

PubMed

Lorenzo Bermejo, Justo; Rawal, Rajesh; Hemminki, Kari

2004-04-01

Population-based data on the familial association of specific histologic types of ovarian malignancy with other malignancies are limited. Such data may help to elucidate etiologic differences among histologic types of ovarian malignancy. The nationwide Swedish Family-Cancer Database, which includes 10.3 million individuals and 20,974 ovarian carcinomas, was used to calculate standardized incidence ratios and 95% confidence intervals for age- and histology-specific ovarian malignancies in women whose parents or siblings were affected with malignancies at the most common disease sites. Ovarian malignancy was found to be associated with ovarian, laryngeal, breast, endometrial, liver, and colon carcinoma, as well as myeloma; epithelial ovarian malignancy was found to be associated with ovarian, endometrial, and skin malignancies and with melanoma and myeloma; papillary serous cystadenocarcinoma was found to be associated with ovarian and skin malignancies and with myeloma; and endometrioid carcinoma was found to be associated with endometrial, ovarian, and prostate malignancies and with melanoma. For younger women (ages 40-45 years) whose mothers were affected with endometrial malignancies, the risk of developing endometrioid carcinoma was slightly greater than the risk of developing papillary serous cystadenocarcinoma. Specific types of ovarian malignancy may be associated with specific familial disease sites, with such associations depending on age at diagnosis; the strength of the observed associations varied according to histology. Associations were found between endometrioid carcinoma and endometrial malignancy and between serous carcinoma and Hodgkin disease. Copyright 2004 American Cancer Society.

GPER mediates estrogen-induced signaling and proliferations in human breast epithelial cells, and normal and malignant breast

PubMed Central