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1.
Magn Reson Med ; 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38469904

RESUMO

PURPOSE: To develop and validate a noninvasive imaging technique for accurately assessing very slow CSF flow within shunt tubes in pediatric patients with hydrocephalus, aiming to identify obstructions that might impede CSF drainage. THEORY AND METHODS: A simulation of shunt flow enhancement of signal intensity (shunt-FENSI) signal is used to establish the relationship between signal change and flow rate. The quantification of flow enhancement of signal intensity data involves normalization, curve fitting, and calibration to match simulated data. Additionally, a phase sweep method is introduced to accommodate the impact of magnetic field inhomogeneity on the flow measurement. The method is tested in flow phantoms, healthy adults, intensive care unit patients with external ventricular drains (EVD), and shunt patients. EVDs enable shunt-flow measurements to be acquired with a ground truth measure of CSF drainage. RESULTS: The flow-rate-to-signal simulation establishes signal-flow relationships and takes into account the T1 of draining fluid. The phase sweep method accurately accounts for phase accumulation due to frequency offsets at the shunt. Results in phantom and healthy human participants reveal reliable quantification of flow rates using controlled flows and agreement with the flow simulation. EVD patients display reliable measures of flow rates. Shunt patient results demonstrate feasibility of the method and consistent flow rates for functional shunts. CONCLUSION: The results demonstrate the technique's applicability, accuracy, and potential for diagnosing and noninvasively monitoring hydrocephalus. Limitations of the current approach include a high sensitivity to motion and strict requirement of imaging slice prescription.

2.
Neurooncol Adv ; 4(1): vdac033, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35386568

RESUMO

Background: Treatment of metastatic brain tumors often involves radiotherapy with or without surgical resection as the first step. However, the indications for when to use surgery are not clearly defined for certain tumor sizes and multiplicity. This study seeks to determine whether resection of brain metastases versus exclusive radiotherapy provided improved survival and local control in cases where metastases are limited in number and diameter. Methods: According to PRISMA guidelines, this meta-analysis compares outcomes from treatment of a median number of brain metastases ≤ 4 with a median diameter ≤ 4 cm with exclusive radiotherapy versus surgery followed by radiotherapy. Four randomized control trials and 11 observational studies (1693 patients) met inclusion criteria. For analysis, studies were grouped based on whether radiation involved stereotactic radiosurgery (SRS) or whole-brain radiotherapy (WBRT). Results: In both analyses, there was no difference in survival between surgery ± SRS versus SRS alone two years after treatment (OR 1.89 (95% CI: 0.47-7.55, P = .23) or surgery + WBRT versus radiotherapy alone (either WBRT and/or SRS) (OR 1.18 (95% CI: 0.76-1.84, P = .46). However, surgical patients demonstrated greater risk for local tumor recurrence compared to SRS alone (OR 2.20 (95% CI: 1.49-3.25, P < .0001)) and compared to WBRT/SRS (OR 2.93; 95% CI: 1.68-5.13, P = .0002). Conclusion: The higher incidence of local tumor recurrence for surgical patients suggests that more prospective studies are needed to clarify outcomes for treatment of 1-4 metastasis less than 4 cm diameter.

3.
Childs Nerv Syst ; 37(8): 2695-2698, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33030603

RESUMO

The authors describe a follow-up to a case of a 19-year-old female with shunted aqueductal stenosis who presented with low-pressure hydrocephalus during a shunt malfunction. Shortly after management with CSF drainage at negative pressure, a magnetic resonance elastography scan was performed and revealed very low brain stiffness (high compliance). Here we present the case of the same patient seen 2 years later, now 21 years old, who again received a magnetic resonance elastography scan after receiving treatment for another shunt malfunction, this time with high intracranial pressure. This scan revealed recovery of brain stiffness to a near normal value for the patients' age. This observation suggests the low brain stiffness observed during the low-pressure hydrocephalus event is reversible. The authors discuss these findings in relation to biomechanical hypotheses of low-pressure hydrocephalus.


Assuntos
Hidrocefalia de Pressão Normal , Hidrocefalia , Adulto , Encéfalo/diagnóstico por imagem , Aqueduto do Mesencéfalo , Derivações do Líquido Cefalorraquidiano , Drenagem , Feminino , Humanos , Hidrocefalia/complicações , Hidrocefalia/diagnóstico por imagem , Hidrocefalia de Pressão Normal/diagnóstico por imagem , Hidrocefalia de Pressão Normal/cirurgia , Pressão Intracraniana , Adulto Jovem
6.
J Clin Neurosci ; 42: 129-133, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28342701

RESUMO

With the aging population, the incidence of chronic subdural hematoma (CSDH) is expected to rise. Once symptomatic the morbidity from CSDH is not insignificant. We studied patients who had a minor head injury and CT brain scan prior to developing CSDH to determine if there were any predictors on these scans for subsequent development of a CSDH. A retrospective review was performed on all patients operated for CSDH over a 3-year period and a review performed on those who had imaging studies at the time of a preceding minor head injury. Seven of 37 patients had CT scans prior to developing CSDH. All had evidence of small increases in CSF intensity on the side or sides of the subsequent CSDH. In conclusion, in those patients with a history of minor head injury prior to developing a CSDH, CT brain demonstrated small increases in cerebral spinal fluid (CSF) intensity on the side or sides of the subsequent CSDH. Recognizing this finding may be helpful in monitoring these patients or initiating medical therapy.


Assuntos
Traumatismos Craniocerebrais/diagnóstico por imagem , Hematoma Subdural Crônico/diagnóstico por imagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Traumatismos Craniocerebrais/líquido cefalorraquidiano , Traumatismos Craniocerebrais/complicações , Feminino , Hematoma Subdural Crônico/líquido cefalorraquidiano , Hematoma Subdural Crônico/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Tomografia Computadorizada por Raios X
7.
Pediatr Neurosurg ; 51(5): 257-62, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27198914

RESUMO

The authors describe the case of a 19-year-old female with shunted aqueductal stenosis who presented with low-pressure hydrocephalus that responded to negative pressure drainage. A magnetic resonance elastography scan performed 3 weeks later demonstrated very low brain tissue stiffness (high brain tissue compliance). An analysis of the importance of this finding in understanding this rare condition is discussed.


Assuntos
Encéfalo/diagnóstico por imagem , Técnicas de Imagem por Elasticidade/métodos , Hidrocefalia/diagnóstico por imagem , Feminino , Humanos , Masculino , Adulto Jovem
8.
Case Rep Neurol Med ; 2014: 395196, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25478260

RESUMO

Objective. A rare case of myeloid sarcoma (MS), previously referred to as granulocytic sarcoma or chloroma, is presented. Representing a unique form of acute myeloid leukemia (AML), MS may rarely occur in adults. Even rarer, MS may occur as the initial presentation of AML. Methods. We report a singular and illustrative case of an orbital pseudotumor mimicking mass in a 65-year-old male as the initial presentation of AML. Results. Neurosurgical intervention was required to establish the definitive diagnosis via right modified orbitofrontozygomatic craniotomy as well as to decompress the optic canal, superior orbital fissure, and orbit. Conclusion. Postoperatively, he reported decreased pain and improvement of his vision. Further examination revealed decreased proptosis and improved extraocular mobility. Pathological findings demonstrated MS. We review the literature and discuss the neurosurgical relevance of MS as the initial presentation of AML.

9.
J Neurosurg Spine ; 21(5): 833-6, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25216402

RESUMO

Patients with Marfan syndrome used to succumb early in life from cardiovascular complications. With the current rapid advance in medical and surgical care, such patients may now have near-normal longevities. Consequently, rare late-life complications are emerging in these patients and represent challenges to clinicians for their diagnoses and treatments. The authors report a rare case of pelvic pain and genital prolapse from a giant presacral Tarlov cyst in a 67-year-old patient with Marfan syndrome. This 67-year-old Caucasian female presented with progressively severe pelvic pain, intermittent explosive diarrhea, and dysuria. Physical and bimanual examination demonstrated genital prolapse and a nontender, cyst-like mass fixed in the midline. She underwent ultrasound, CT, and eventually MRI evaluations that led to the diagnosis of a giant (6.7 × 6.4 × 6.6 cm) Tarlov cyst originating from the right S-2 nerve root sleeve/sacral foramen with intrapelvic extension. She underwent S1-S2 and S2-S3 laminectomy with obliteration of the Tarlov cyst using aneurysm clips. Postoperatively, her pelvic pain and bowel symptoms resolved and the bladder symptoms improved. The 3-month follow-up CT of abdomen/pelvis demonstrated resolution of the cyst. The present case illustrates that clinicians caring for elderly patients with Marfan syndrome need to increasingly recognize such unusual late-life complications. Also, these large Tarlov cysts can be simply and effectively obliterated with aneurysm clips.


Assuntos
Síndrome de Marfan/complicações , Dor Pélvica/etiologia , Dor Pélvica/cirurgia , Instrumentos Cirúrgicos , Cistos de Tarlov/complicações , Cistos de Tarlov/cirurgia , Idoso , Feminino , Humanos , Laminectomia , Imageamento por Ressonância Magnética , Dor Pélvica/diagnóstico , Cistos de Tarlov/diagnóstico , Tomografia Computadorizada por Raios X
10.
Neuroimage ; 79: 145-52, 2013 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-23644001

RESUMO

The noninvasive measurement of the mechanical properties of brain tissue using magnetic resonance elastography (MRE) has emerged as a promising method for investigating neurological disorders. To date, brain MRE investigations have been limited to reporting global mechanical properties, though quantification of the stiffness of specific structures in the white matter architecture may be valuable in assessing the localized effects of disease. This paper reports the mechanical properties of the corpus callosum and corona radiata measured in healthy volunteers using MRE and atlas-based segmentation. Both structures were found to be significantly stiffer than overall white matter, with the corpus callosum exhibiting greater stiffness and less viscous damping than the corona radiata. Reliability of both local and global measures was assessed through repeated experiments, and the coefficient of variation for each measure was less than 10%. Mechanical properties within the corpus callosum and corona radiata demonstrated correlations with measures from diffusion tensor imaging pertaining to axonal microstructure.


Assuntos
Corpo Caloso/fisiologia , Corpo Caloso/ultraestrutura , Imagem de Tensor de Difusão/métodos , Técnicas de Imagem por Elasticidade/métodos , Fibras Nervosas Mielinizadas/fisiologia , Fibras Nervosas Mielinizadas/ultraestrutura , Adulto , Módulo de Elasticidade/fisiologia , Voluntários Saudáveis , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Resistência à Tração/fisiologia , Adulto Jovem
11.
J Neurosurg Pediatr ; 11(4): 451-3, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23394353

RESUMO

Isolated unilateral temporalis muscle hypertrophy is an extremely rare cause of swelling in the temple region, with only 7 cases reported in the literature. The authors report the eighth case of this unique occurrence in a 17-year-old boy and review the current literature.


Assuntos
Doenças Musculares/patologia , Músculo Temporal/patologia , Adolescente , Humanos , Hipertrofia/diagnóstico , Hipertrofia/etiologia , Hipertrofia/terapia , Masculino , Doenças Musculares/etiologia , Doenças Musculares/terapia
12.
J Surg Case Rep ; 2013(5)2013 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-24964444

RESUMO

Cerebral venous thrombosis (CVT) remains a diagnostic and therapeutic challenge for clinicians. Manifesting in a remarkably wide spectrum of symptoms and signs, CVT often presents in a misleading fashion-if unrecognized or misdiagnosed, it carries potentially fatal consequences. Visual loss is quite rare as the initial presentation of CVT and is typically a finding more frequent in chronic cases with associated papilledema on funduscopy Ferro, Lopes, Rosas and Fontes (Delay in Hospital Admission of Patients with Cerebral Vein and Dural Sinus Thrombosis. Cerebrovasc Dis 2005;19: :152-6). We report a rare case of acute cortical blindness as the initial presentation of CVT in an 18-year-old female patient and review the current literature.

13.
World Neurosurg ; 77(1): 202.e1-3, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22405398

RESUMO

BACKGROUND: Percutaneous balloon rhizotomy is one of the standard techniques for the treatment of trigeminal neuralgia. However, there have been well-reported complications from cannulating the foramen ovale (FO). We describe a novel technique for cannulating the FO using 3-dimensional (3D) rotational fluoroscopy. METHODS: Three-dimensional rotational fluoroscopy is used to reconstruct the skull base. The optimal working projection is thus generated to best visualize the FO. When the optimal working projection is not anatomically feasible, for example, in a patient with severe cervical spondylosis, further rotational fluoroscopic data acquisition can assess the position of the needle to determine its relationship to the foramen. Furthermore, while inflated, the balloon position can also be verified with the same rotational technique. RESULTS: Three-dimensional rotational fluoroscopy allows quick, safe, and easy cannulation of the FO. The equipment is readily available in the biplanar fluoroscopy suite. Its use should decrease the incidence of complications reported with the standard fluoroscopic technique. CONCLUSIONS: Three-dimensional rotational fluoroscopy allows real-time visual guidance to cannulate the FO and determine the optimal position of the inflated balloon. We believe that this is an important adjunct for treating trigeminal neuralgia via percutaneous techniques.


Assuntos
Fluoroscopia/métodos , Procedimentos Neurocirúrgicos/métodos , Rizotomia/métodos , Cirurgia Assistida por Computador/métodos , Neuralgia do Trigêmeo/cirurgia , Idoso , Cateterismo , Demência/complicações , Feminino , Forame Oval/diagnóstico por imagem , Forame Oval/cirurgia , Humanos , Processamento de Imagem Assistida por Computador , Imageamento Tridimensional , Recidiva , Base do Crânio/diagnóstico por imagem , Base do Crânio/cirurgia , Espondilose/complicações , Espondilose/cirurgia
14.
Magn Reson Imaging ; 30(2): 205-12, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22055750

RESUMO

In magnetic resonance elastography (MRE), shear waves at a certain frequency are encoded through bipolar gradients that switch polarity at a controlled encoding frequency and are offset in time to capture wave propagation using a controlled sampling frequency. In brain MRE, there is a possibility that the mechanical actuation frequency is different from the vibration frequency, leading to a mismatch with encoding and sampling frequencies. This mismatch can occur in brain MRE from causes both extrinsic and intrinsic to the brain, such as scanner bed vibrations or active damping in the head. The purpose of this work was to investigate how frequency mismatch can affect MRE shear stiffness measurements. Experiments were performed on a dual-medium agarose gel phantom, and the results were compared with numerical simulations to quantify these effects. It is known that off-frequency encoding alone results in a scaling of wave amplitude, and it is shown here that off-frequency sampling can result in two main effects: (1) errors in the overall shear stiffness estimate of the material on the global scale and (2) local variations appearing as stiffer and softer structures in the material. For small differences in frequency, it was found that measured global stiffness of the brain could theoretically vary by up to 12.5% relative to actual stiffness with local variations of up to 3.7% of the mean stiffness. It was demonstrated that performing MRE experiments at a frequency other than that of tissue vibration can lead to artifacts in the MRE stiffness images, and this mismatch could explain some of the large-scale scatter of stiffness data or lack of repeatability reported in the brain MRE literature.


Assuntos
Algoritmos , Encéfalo/anatomia & histologia , Técnicas de Imagem por Elasticidade/métodos , Aumento da Imagem/métodos , Interpretação de Imagem Assistida por Computador/métodos , Técnicas de Imagem por Elasticidade/instrumentação , Humanos , Imagens de Fantasmas , Reprodutibilidade dos Testes , Tamanho da Amostra , Sensibilidade e Especificidade , Processamento de Sinais Assistido por Computador
15.
Magn Reson Med ; 62(4): 1007-16, 2009 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-19645009

RESUMO

Diffusion tensor imaging of localized anatomic regions, such as brainstem, cervical spinal cord, and optic nerve, is challenging because of the existence of significant susceptibility differences, severe physiologic motion in the surrounding tissues, and the need for high spatial resolution to resolve the underlying complex neuroarchitecture. The aim of the methodology presented here is to achieve high-resolution diffusion tensor imaging in localized regions of the central nervous system that is motion insensitive and immune to susceptibility while acquiring a set of two-dimensional images with more than six diffusion encoding directions within a reasonable total scan time. We accomplish this aim by implementing self-navigated, multishot, variable-density, spiral encoding with outer volume suppression. We establish scan protocols for achieving equal signal-to-noise ratio at 1.2 mm and 0.8 mm in-plane resolution for reduced field-of-view diffusion tensor imaging of the brainstem. In vivo application of the technique on the human pons of three subjects shows a clear delineation of the multiple local neural tracts. By comparing scans acquired with varying in-plane resolution but with constant signal-to-noise ratio, we demonstrate that increasing the resolution and reducing the partial volume effect result in higher fractional anisotropy values for the corticospinal tracts.


Assuntos
Algoritmos , Imagem de Difusão por Ressonância Magnética/métodos , Aumento da Imagem/métodos , Interpretação de Imagem Assistida por Computador/métodos , Imageamento Tridimensional/métodos , Ponte/anatomia & histologia , Humanos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
16.
J Spinal Disord Tech ; 22(3): 202-6, 2009 May.
Artigo em Inglês | MEDLINE | ID: mdl-19412023

RESUMO

STUDY DESIGN: A retrospective review was performed to determine the outcomes of patients with cauda equina syndrome (CES) from a herniated lumbar disc at our institutions. OBJECTIVE: CES from lumbar herniated discs is considered the only absolute indication for surgery. It is considered a neurosurgical emergency with the outcome related to how quickly it is diagnosed and treated. The results of recovery of bladder function are felt by many authors to be related to early diagnosis and surgical intervention. Most authors recommend a wide decompressive laminectomy when surgery is performed. We reviewed our cases to determine if they conformed to these assumptions. SUMMARY OF BACKGROUND DATA: Although many articles regarding the outcome of CES from herniated lumbar discs suggest that early surgery is superior to surgery that is delayed, others have demonstrated no correlation between time-to-surgery and chances for recovery of neurologic and bladder function. METHODS: A retrospective review of all patients with lumbar herniated discs and CES from the years 1985 to 2004 was carried out. There were 31 patients, 28 of whom had bladder incontinence or retention requiring catheterization. Six patients were operated within 24 hours, 8 between 24 and 48 hours, and 17 after 48 hours (range: 60 h to 2 wk). Average follow-up was 5 years. RESULTS: Twenty-seven of these patients regained continence not requiring catheterization. There was no correlation between the time-to-surgery and recovery of bladder function. There was also no correlation between the time-to-surgery and recovery of motor and sensory function. The majority of patients underwent unilateral hemilaminotomy or bilateral hemilaminotomies; decompressive laminectomy was reserved for patients with underlying spinal stenosis or posteriorly herniated fragments. All of the patients were relieved of their radicular pain. CONCLUSIONS: In our series of patients with CES and bladder incontinence or retention, over 90% regained continence. Recovery of function was not related to the time to surgical intervention. The majority of the patients were adequately treated without the need for a complete laminectomy.


Assuntos
Cauda Equina/patologia , Deslocamento do Disco Intervertebral/complicações , Deslocamento do Disco Intervertebral/patologia , Vértebras Lombares/patologia , Polirradiculopatia/etiologia , Polirradiculopatia/patologia , Adulto , Idoso , Cauda Equina/fisiopatologia , Cauda Equina/cirurgia , Descompressão Cirúrgica/métodos , Descompressão Cirúrgica/estatística & dados numéricos , Serviços Médicos de Emergência/normas , Serviços Médicos de Emergência/estatística & dados numéricos , Feminino , Humanos , Laminectomia/métodos , Laminectomia/estatística & dados numéricos , Vértebras Lombares/cirurgia , Masculino , Pessoa de Meia-Idade , Procedimentos Neurocirúrgicos/métodos , Procedimentos Neurocirúrgicos/estatística & dados numéricos , Avaliação de Resultados em Cuidados de Saúde , Polirradiculopatia/fisiopatologia , Radiculopatia/etiologia , Radiculopatia/fisiopatologia , Radiculopatia/cirurgia , Recuperação de Função Fisiológica/fisiologia , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento , Bexiga Urinaria Neurogênica/etiologia , Bexiga Urinaria Neurogênica/fisiopatologia , Bexiga Urinaria Neurogênica/cirurgia , Cateterismo Urinário/estatística & dados numéricos , Adulto Jovem
17.
Artigo em Inglês | MEDLINE | ID: mdl-19164026

RESUMO

Diffusion Tensor Imaging (DTI) of localized anatomical regions (i.e brainstem, cervical spinal cord, and optic nerve) is challenging because of the existence of significant susceptibility differences in the surrounding tissues, their high motion sensitivity and the need for high spatial resolution to resolve the underlying complex histoarchitecture. The aim of the present methodology is to achieve high resolution DTI with motion compensating capability in localized regions of the central nervous system. We accomplish this by implementing self-navigated multi-shot variable density spiral encoding with outer volume suppression. In vivo application of the technique on the human brainstem demonstrates a clear delineation of the multiple local neural tracts. We also investigate the partial volume effect on the extracted diffusion anisotropy metrics by varying the in-plane resolution while maintaining a constant signal-to-noise ratio.


Assuntos
Algoritmos , Inteligência Artificial , Imagem de Difusão por Ressonância Magnética/métodos , Interpretação de Imagem Assistida por Computador/métodos , Fibras Nervosas Mielinizadas/ultraestrutura , Reconhecimento Automatizado de Padrão/métodos , Ponte/anatomia & histologia , Humanos , Aumento da Imagem/métodos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
18.
J Neurosurg ; 107(4): 805-8, 2007 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-17937227

RESUMO

OBJECT: Gamma Knife surgery has recently been used to treat patients with cluster headaches. Both the trigeminal nerve root and the pterygopalatine ganglion (PPG) have been targeted. However, there are no clear-cut anatomical landmarks on computed tomography (CT) scans or magnetic resonance images that accurately identify the PPG. Therefore, the authors performed microsurgical dissections on latex-injected cadaver heads to expose the PPG and correlated the findings with thin-slice axial CT scans obtained in the same heads to determine how best to target the PPG. METHODS: Three cadaver heads (five sides) previously injected with colored latex were dissected using skull base approaches and microsurgical techniques to identify the PPG and surrounding structures. Measurements were then made to different osseous anatomical landmarks such as the foramen rotundum, vidian canal, and so on. The PPG was marked with a radiopaque marker and thin-slice CT scans were obtained in the cadaver heads to develop some correlates that could be used to identify where the PPG is located on CT scans. RESULTS: The PPG was clearly identified in all specimens and had a mean diameter of 3.58 +/- 0.6 mm. The PPG was always located in the same plane (lateral and vertical) as the vidian canal and was located on average 2.7 +/- 0.3 mm from the end of the canal. The vidian canal was clearly identified on coronal CT scans and had a diameter of 3.05 mm. CONCLUSIONS: There was a clear and constant relationship between the PPG and vidian canal. The vidian canal is easily identified on coronal CT scans and can be used as a landmark to target the PPG with the Gamma Knife.


Assuntos
Cefaleia Histamínica/diagnóstico por imagem , Cefaleia Histamínica/cirurgia , Gânglios Parassimpáticos/diagnóstico por imagem , Gânglios Parassimpáticos/cirurgia , Radiocirurgia/métodos , Tomografia Computadorizada por Raios X , Cadáver , Gânglios Parassimpáticos/anatomia & histologia , Humanos , Látex , Microdissecção , Nervo Trigêmeo/anatomia & histologia , Nervo Trigêmeo/diagnóstico por imagem , Nervo Trigêmeo/cirurgia
19.
Int J Oncol ; 31(5): 1039-50, 2007 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-17912429

RESUMO

Malignant meningiomas are highly aggressive and frequently recur after surgical resection of the tumor. Earlier studies have reported that the cysteine protease cathepsin B and the matrix metalloproteinase MMP-9 play important roles in tumor progression. In the present study, we made an attempt to evaluate the roles of these proteases in the malignant meningioma tumor microenvironment and determined the effectiveness of using single or bicistronic siRNA constructs for cathepsin B and MMP-9, in both in vitro and in vivo models. Transfection of a plasmid vector expressing double-stranded RNA for cathepsin B and MMP-9 significantly inhibited mRNA and protein levels of cathepsin B and MMP-9. The migration and invasion of meningioma cells were decreased after treatment with single or bicistronic siRNA constructs for cathepsin B and MMP-9 compared to controls and vector controls. Inhibition of angiogenesis was observed when the cells were transfected with single or bicistronic constructs for cathepsin B and MMP-9, when compared to controls or empty vector controls. Our study revealed that abrogation of cathepsin B and MMP-9 expression decreased the activation of major proteins involved in MAP kinase and PI3 kinase pathways indicating that targeting these proteases may hinder intracellular signaling and thus decrease cell survival and proliferation in malignant meningiomas. In addition to the in vitro evidence, we observed a significant regression of pre-established orthotopic tumors after treatment with RNAi plasmid vectors targeting cathepsin B and MMP-9. Furthermore, these observations demonstrate that the simultaneous RNAi-mediated targeting of cathepsin B and MMP-9 has potential application for the treatment of human meningiomas.


Assuntos
Catepsina B/genética , Metaloproteinase 9 da Matriz/genética , Neoplasias Meníngeas/terapia , Meningioma/terapia , Neovascularização Patológica/prevenção & controle , Interferência de RNA , Animais , Linhagem Celular Tumoral , MAP Quinases Reguladas por Sinal Extracelular/fisiologia , Humanos , Sistema de Sinalização das MAP Quinases/fisiologia , Neoplasias Meníngeas/irrigação sanguínea , Neoplasias Meníngeas/enzimologia , Neoplasias Meníngeas/patologia , Meningioma/irrigação sanguínea , Meningioma/enzimologia , Meningioma/patologia , Camundongos , Invasividade Neoplásica
20.
Clin Cancer Res ; 13(14): 4051-60, 2007 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-17634529

RESUMO

PURPOSE: The purpose of this study was to evaluate the therapeutic potential of using plasmid-expressed RNA interference (RNAi) targeting urokinase-type plasminogen activator (uPA) receptor (uPAR) and uPA to treat human glioma. EXPERIMENTAL DESIGN: In the present study, we have used plasmid-based RNAi to simultaneously down-regulate the expression of uPAR and uPA in SNB19 glioma cell lines and epidermal growth factor receptor (EGFR)--overexpressing 4910 human glioma xenografts in vitro and in vivo, and evaluate the i.p. route for RNAi-expressing plasmid administered to target intracranial glioma. RESULTS: Plasmid-mediated RNAi targeting uPAR and uPA did not induce OAS1 expression as seen from reverse transcription-PCR analysis. In 4910 EGFR-overexpressing cells, down-regulation of uPAR and uPA induced the down-regulation of EGFR and vascular endothelial growth factor and inhibited angiogenesis in both in vitro and in vivo angiogenic assays. In addition, invasion and migration were inhibited as indicated by in vitro spheroid cell migration, Matrigel invasion, and spheroid invasion assays. We did not observe OAS1 expression in mice with preestablished intracranial tumors, which were given i.p. injections of plasmid-expressing small interfering RNA--targeting uPAR and uPA. Furthermore, the small interfering RNA plasmid targeting uPAR and uPA caused regression of preestablished intracranial tumors when compared with the control mice. CONCLUSION: In conclusion, the plasmid-expressed RNAi targeting uPAR and uPA via the i.p. route has potential clinical applications for the treatment of glioma.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Neoplasias Encefálicas/patologia , Plasmídeos , Interferência de RNA , Receptores de Superfície Celular/genética , Ativador de Plasminogênio Tipo Uroquinase/genética , Animais , Neoplasias Encefálicas/prevenção & controle , Linhagem Celular Tumoral , Glioma/prevenção & controle , Humanos , Injeções Intraperitoneais , Camundongos , Camundongos Nus , Transplante de Neoplasias , RNA Interferente Pequeno/genética , Receptores de Ativador de Plasminogênio Tipo Uroquinase , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transplante Heterólogo
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