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1.
J Neurosurg ; 140(2): 412-419, 2024 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-37542442

RESUMEN

OBJECTIVE: The endoscopic transorbital approach (ETOA) and transorbital anterior clinoidectomy have been suggested as novel procedures through which to reach the superolateral compartments of the orbit, allowing optic canal decompression. However, there is limited literature describing the technical details and surgical outcomes of these procedures. In this study, the authors aimed to analyze the feasibility and efficacy of endoscopic transorbital decompression of the optic canal through anterior clinoidectomy for compressive optic neuropathic lesions. METHODS: Between 2016 and 2022, the authors performed ETOA for compressive optic neuropathic lesions in 14 patients. All these patients underwent transorbital anterior clinoidectomy through the surgically defined "intraorbital clinoidal triangle," which is composed of the roof of the superior orbital fissure, the medial margin of the optic canal, the medial border of the superior orbital fissure, and the optic strut. Demographic data, tumor characteristics, pre- and postoperative imaging, pre- and postoperative visual examinations, and surgical outcomes were retrospectively reviewed. RESULTS: The mean age at the time of ETOA was 53.3 years (range 41-64 years), and the mean follow-up was 16.8 months (range 6.7-51.4 months). The inclusion criterion in this study was having a meningioma (14 patients). In the preoperative visual function examination, 7 patients with a meningioma showed progressive visual impairment. After endoscopic transorbital optic canal decompression, visual function improved in 5 patients, remained unchanged in 8 patients, and worsened in 1 patient. No new-onset neurological deficit was associated with ETOA and anterior clinoidectomy in any patients. CONCLUSIONS: Endoscopic transorbital decompression of the optic canal with extradural anterior clinoidectomy is a safe and feasible technique that avoids significant injury to the clinoidal internal carotid artery and surrounding neurovascular structures.


Asunto(s)
Neoplasias Meníngeas , Meningioma , Enfermedades del Nervio Óptico , Humanos , Adulto , Persona de Mediana Edad , Meningioma/complicaciones , Meningioma/diagnóstico por imagen , Meningioma/cirugía , Procedimientos Neuroquirúrgicos/métodos , Estudios Retrospectivos , Estudios de Factibilidad , Enfermedades del Nervio Óptico/diagnóstico por imagen , Enfermedades del Nervio Óptico/etiología , Enfermedades del Nervio Óptico/cirugía , Neoplasias Meníngeas/cirugía , Descompresión
2.
J Org Chem ; 88(18): 13315-13326, 2023 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-37668242

RESUMEN

The site-selective modification of quinazolinone as a privileged bicyclic N-heterocycle is an attractive topic in medicinal chemistry and material science. We herein report the ruthenium(II)-catalyzed C-H allylation of 2-aryl quinazolinones with 2-methylidene cyclic carbonate. In addition, tandem C-H allylation and annulation are achieved under rhodium(III) catalysis, resulting in the formation of tetracyclic quinazolinones including a tertiary carbon center. Post-transformations of the synthesized products demonstrate the potential of the developed methodology. A series of mechanistic investigations were also performed.

3.
Materials (Basel) ; 14(14)2021 Jul 16.
Artículo en Inglés | MEDLINE | ID: mdl-34300900

RESUMEN

This study evaluated the mechanical properties and durability performance of latex-modified hybrid fiber-reinforced roller-compacted rapid-set cement concrete (LMHFRCRSC) for emergency repair of concrete pavement. Experimental parameters included the blend ratio of the hybrid fiber, which comprised natural jute fiber (0-0.2 vol.%) and structural synthetic fiber (0-2 vol.%). The mechanical performance of LMHFRCRSC of various blend ratios was evaluated in terms of compressive, flexural, and splitting tensile strength. Durability assessment included chlorine ion penetration and abrasion resistance measurements. Compressive and flexural strength values of 21 and 3.5 MPa, respectively, were the set targets after 4 h of curing; a compressive strength of 35 MPa, a flexural strength of 4.5 MPa, a splitting tensile strength of 4.2 MPa, and chloride ion penetration of 2000 C or less were required after 28 days of curing. Our test results confirmed that all mix proportions satisfied the target values, regardless of the blend ratio of the hybrid fiber. Specifically, the mechanical performance of the concrete improved as the blend ratio of the structural synthetic fiber increased. With regard to durability, a greater amount of jute fiber, a hydrophilic fiber, enhanced the concrete's durability. Additionally, incorporating jute fiber of 0.6 kg/m3 provided excellent chlorine ion penetration resistance. The optimal blend ratio for the hybrid fiber was natural jute fiber at 0.6 kg/m3 and structural synthetic fiber at 13.65 kg/m3 (mix: J0.6 + P13.65); with this mix proportion, a chloride ion penetration amount of 1000 C or less and maximum mechanical performance were achieved.

4.
Artículo en Inglés | MEDLINE | ID: mdl-32849307

RESUMEN

Background/Purpose: A prolactinoma is the most common pituitary adenoma, but it is relatively rare in childhood and adolescence. There is only limited research about the clinical spectrum, treatment, and outcomes of prolactinomas in childhood and adolescence. In this single-center cohort study, we assessed the clinical, hormonal, and neuroradiological characteristics and therapeutic outcomes of children and adolescents with prolactinomas. Methods: This retrospective cohort study included 25 patients with prolactinomas diagnosed before 19 years of age, who presented at Samsung Medical Center during a 15-year period (March 2005 to August 2019). Results: The median age at diagnosis was 16.9 (range 10.1-18.5) years, and 80% of the patients were female. The common clinical manifestations at diagnosis were galactorrhea (10/20, 50%) and amenorrhea (9/20, 45%) among females and visual field defects (3/5, 60%) and headaches (2/5, 40%) among males. In our cohort, macroadenomas accounted for 56% of cases, and the rate of overall responsiveness to dopamine agonists (DAs) was 56% (10/18). Male gender, the prolactin (PRL) level at diagnosis, and the presence of panhypopituitarism were positively correlated with maximum tumor diameter (r = 0.443, P = 0.026; r = 0.710, P < 0.001; and r = 0.623, P = 0.001, respectively). After the trans-sphenoidal approach (TSA), 53% (8/15) of patients showed normalization of the PRL level. Three patients, who underwent gamma knife surgery (GKS) owing to either resistance or intolerance to DAs or recurrence after the TSA, achieved a normal PRL level accompanied with marked tumor reduction and symptom remission. Conclusions: A macroprolactinoma is more prevalent than a microprolactinoma in children and adolescents than in adults. Male gender, increased PRL levels, and the presence of panhypopituitarism at diagnosis are closely related to macroprolactinomas in children and adolescents.


Asunto(s)
Adenoma/patología , Amenorrea/patología , Bromocriptina/uso terapéutico , Galactorrea/patología , Neoplasias Hipofisarias/patología , Prolactinoma/patología , Trastornos de la Visión/patología , Adenoma/diagnóstico por imagen , Adenoma/tratamiento farmacológico , Adenoma/metabolismo , Adolescente , Adulto , Amenorrea/diagnóstico por imagen , Amenorrea/tratamiento farmacológico , Amenorrea/metabolismo , Niño , Agonistas de Dopamina/uso terapéutico , Femenino , Estudios de Seguimiento , Galactorrea/diagnóstico por imagen , Galactorrea/tratamiento farmacológico , Galactorrea/metabolismo , Humanos , Masculino , Neoplasias Hipofisarias/diagnóstico por imagen , Neoplasias Hipofisarias/tratamiento farmacológico , Neoplasias Hipofisarias/metabolismo , Prolactina/metabolismo , Prolactinoma/diagnóstico por imagen , Prolactinoma/tratamiento farmacológico , Prolactinoma/metabolismo , Estudios Retrospectivos , Resultado del Tratamiento , Trastornos de la Visión/diagnóstico por imagen , Trastornos de la Visión/tratamiento farmacológico , Trastornos de la Visión/metabolismo , Adulto Joven
5.
J Craniomaxillofac Surg ; 47(1): 158-164, 2019 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-30497950

RESUMEN

PURPOSE: Systematic examination of increased intracranial pressure (ICP) is important during the follow-up period after surgical repair of syndromic craniosynostosis. In these patients, postoperative progress can be unclear due to the involvement of multiple sutures and the high incidence of relapse due to the progressive nature of the disease and to genetic variability. In this study, we investigated the clinical manifestations of increased ICP in syndromic craniosynostosis patients before and after surgery. MATERIALS AND METHODS: We collected pre- and post-operative data from patients with syndromic craniosynostosis from January 2004 and December 2014 on the clinical manifestations of increased ICP, namely, the presence of 1) subjective symptoms, 2) visual disturbances and papilledema, 3) thumbprinting phenomenon (beaten copper appearance) on skull x-ray, and 4) hydrocephalus on computed tomography. RESULTS: A total of 17 syndromic craniosynostosis patients were included in this study, and three distinct patterns of disease progress were noted. Among all patients who underwent cranioplasty, the significant finding with regards to clinical manifestations was amelioration of the beaten copper appearance on skull x-ray after surgery. Likewise, among patients with recurrent increased ICP during the postoperative follow-up period, numerous clinical manifestations were noted, including subjective symptoms (33.3%), papilledema (50%), ventricular dilation (66.6%), and a beaten copper appearance on skull x-ray (100%). CONCLUSION: Close monitoring to detect increased ICP is important during follow-up of patients with syndromic craniosynostosis. Among non-invasive methods for indirectly assessing ICP post-operatively, a beaten copper appearance on skull x-ray may be a reliable indicator of increased ICP.


Asunto(s)
Craneosinostosis/complicaciones , Craneosinostosis/cirugía , Papiledema/complicaciones , Papiledema/fisiopatología , Remodelación Ósea , Edema Encefálico/diagnóstico por imagen , Edema Encefálico/patología , Niño , Preescolar , Femenino , Humanos , Hidrocefalia/complicaciones , Lactante , Masculino , Cráneo/diagnóstico por imagen , Cráneo/patología , Cráneo/cirugía , Tomografía Computarizada por Rayos X
6.
J Craniomaxillofac Surg ; 45(11): 1801-1808, 2017 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-28939204

RESUMEN

PURPOSE: "Secondary craniosynostosis" (SCS) refers to a loss of sutures after corrective vault reconstruction. There are no prior studies that comprehensively review SCS in various types of non-syndromic craniosynostosis. We assessed idiopathic and iatrogenic SCS using 3-dimensional computed tomography (3D CT). We also performed a systematic review to estimate the overall incidence of SCS in each craniosynostosis type, and to characterize its clinical features. MATERIALS AND METHODS: We retrospectively reviewed the CT images of patients who underwent surgical correction of craniosynostosis for all types of craniosynostosis between August 1999 and December 2015. A literature search of the Medline and Ovid databases was conducted in October 2016 using the search term "secondary craniosynostosis." RESULTS: In our series, iatrogenic SCS was observed in all patients who had manipulated normal patent sutures to variable extents. Three (17.6%) cases of idiopathic SCS developed on sagittal sutures, and were confirmed with a 12-month follow-up CT. In a pooled analysis of 10 articles, overall SCS developed in 123 of 1205 patients (10.2%). Iatrogenic SCS cases made up 87 of 1205 cases (7.2%), whereas 38 (3.1%) were idiopathic. Idiopathic SCS most commonly developed at the bi-coronal suture (n = 32, 84.2%), followed by the sagittal suture (n = 4, 10.5%) and uni-coronal suture (n = 1, 2.6%). CONCLUSION: This is the first review not only to describe SCS in all types of non-syndromic craniosynostosis, but also to classify SCS into iatrogenic and idiopathic types based on the underlying pathogenesis.


Asunto(s)
Suturas Craneales/cirugía , Craneosinostosis/cirugía , Niño , Preescolar , Suturas Craneales/diagnóstico por imagen , Craneosinostosis/clasificación , Craneosinostosis/diagnóstico por imagen , Craneotomía/métodos , Femenino , Humanos , Enfermedad Iatrogénica , Imagenología Tridimensional , Lactante , Masculino , Recurrencia , Reoperación , Estudios Retrospectivos , Tomografía Computarizada por Rayos X
7.
J Korean Neurosurg Soc ; 59(3): 197-203, 2016 May.
Artículo en Inglés | MEDLINE | ID: mdl-27226849

RESUMEN

Craniosynostosis is defined as the premature fusion of one or more cranial sutures resulting in skull deformity. Characteristically, this disorder can cause diverse neurosurgical problems, as well as abnormal skull shape. Intracranial hypertension, hydrocephalus, Chiari malformation and neuropsychological dysfunction are the major neurosurgical concerns in children with craniosynostosis. In this review article, we investigate pathophysiology, characteristics and proper neurosurgical management of these neurosurgical issues, respectively.

8.
Ann Clin Lab Sci ; 44(2): 213-6, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-24795062

RESUMEN

Mutations in the glutaryl-CoA dehydrogenase gene can result in Glutaric aciduria type 1(GA 1) by accumulation of glutaric acid, 3-hydroxyglutaric acid (3-OH-GA), and glutarylcarnitine (C5DC). GA 1 is characterized by macrocephaly, subdural hemorrhage (SDH), and dystonic movement disorder after acute encephalopathic crisis. We report a Korean patient with GA1 and a novel mutation. A 16-month-old boy presented with SDH, macrocephaly, and developmental delay. In the neurologic examination, the patient had mild axial hypotonia, but otherwise normal neurologic functions. The brain MRI showed large amounts of bilateral SDH and high signal intensity in both basal ganglia and thalamus. Metabolic screening tests detected highly elevated urinary GA levels but 3-OH-glutaric acid was normal. C5DC was 0.94 µM/L (reference range < 0.3 µM/L). The patient had compound heterozygous mutations of the GCDH gene: p.Arg257Gln (c.770G>A) and p.Cys308Arg (c.922T>C). p.Cys308Arg is a novel mutation; reports of p.Arg257Gln were also rare both in Caucasians and Asian populations. In summary, we hereby report one Korean patient with GA1 with clinical, biochemical, and radiologic characteristics confirmed by genetic analysis.


Asunto(s)
Errores Innatos del Metabolismo de los Aminoácidos/enzimología , Errores Innatos del Metabolismo de los Aminoácidos/genética , Pueblo Asiatico/genética , Encefalopatías Metabólicas/enzimología , Encefalopatías Metabólicas/genética , Glutaril-CoA Deshidrogenasa/deficiencia , Glutaril-CoA Deshidrogenasa/genética , Mutación Missense/genética , Errores Innatos del Metabolismo de los Aminoácidos/diagnóstico por imagen , Secuencia de Bases , Encéfalo/enzimología , Encéfalo/patología , Encefalopatías Metabólicas/diagnóstico por imagen , Preescolar , Análisis Mutacional de ADN , Humanos , Lactante , Imagen por Resonancia Magnética , Masculino , Datos de Secuencia Molecular , República de Corea , Tomografía Computarizada por Rayos X
9.
Pediatr Neurol ; 46(4): 222-4, 2012 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-22490766

RESUMEN

Tuberous sclerosis complex is a genetic disorder caused by mutations in the genes TSC1 or TSC2. Studies of these mutations are very rare in Korean populations. A previous study identified mutations in only 30% of patients by denaturing high performance liquid chromatography with sequencing. Here, we sought to determine the mutational frequency in Koreans. Eleven patients who fulfilled the diagnostic criteria for tuberous sclerosis complex were included. All patients underwent sequencing of both TSC genes, and if no mutations were evident, multiplex ligation-dependent probe amplification was performed. Mutations were detected by sequencing in 82% (9/11) of patients: 36.4% (4/11) in TSC1 and 45.5% (5/11) in TSC2. Two patients with no mutations carried large deletions that included exon 1 of TSC1 in one patient and exons 1-15 of TSC2 in the other patient. Mutations were completely identified in the present study. Therefore, mutation rates in Korean patients may not be lower than those in other ethnic groups. Direct sequencing followed by multiplex ligation-dependent probe amplification analysis may constitute a rational approach to identify disease-causing mutations in Korean patients.


Asunto(s)
Mutación/genética , Esclerosis Tuberosa/genética , Proteínas Supresoras de Tumor/genética , Adolescente , Adulto , Niño , Preescolar , Análisis Mutacional de ADN/métodos , Femenino , Humanos , Lactante , Recién Nacido , Masculino , República de Corea , Esclerosis Tuberosa/diagnóstico , Proteína 1 del Complejo de la Esclerosis Tuberosa , Proteína 2 del Complejo de la Esclerosis Tuberosa , Adulto Joven
10.
Childs Nerv Syst ; 27(11): 1989-94, 2011 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-21779977

RESUMEN

BACKGROUND: To facilitate effective resection of deep-seated brain lesions without causing significant trauma to the overlying cortex, the authors used a transparent plastic tubular retractor to approach these lesions. METHODS: Between July 2009 and January 2011, we used an 11-mm diameter transparent plastic tubular retractor in combination with a frameless stereotactic navigation system to remove 18 deep lesions. RESULTS: Gross total resection of the lesions was achieved in 14 of 18 patients, and subtotal removal occurred in four patients. Effective resection of lesions was achieved in all patients through small size craniotomy window and small cortical incision. The histopathologic diagnosis was established in all 18 patients: 3 hematomas, 3 cavernous angioma, 7 low-grade glioma, 2 dysembryoplastic neuroepithelial tumor, 1 choroid plexus papilloma, 1 abscess, and 1 meningioma. CONCLUSION: Microsurgery using a transparent tubular retractor guided by a neuronavigation system facilitated accurate and effective removal of these deep-seated brain lesions.


Asunto(s)
Encefalopatías/cirugía , Microcirugia/instrumentación , Neuronavegación , Adolescente , Niño , Femenino , Humanos , Masculino
11.
Pediatr Neurosurg ; 45(5): 396-401, 2009.
Artículo en Inglés | MEDLINE | ID: mdl-19940539

RESUMEN

Schwann cells are generally present in the nerve root, not in the spinal cord. Therefore, intramedullary schwannomas are rare and correct preoperative diagnosis is often difficult. To date, less than 50 cases of intramedullary schwannoma with no sign of neurofibromatosis have been reported in the English literature, of which 5 occurred in children. Here, we report a case of primary thoracic intramedullary schwannoma which occurred at the age of 11, confirmed by intraoperative frozen biopsy. The patient presented with decreased sensation below the T6 dermatome at the right side and right lower extremity weakness with urge incontinence. The ideal treatment for intramedullary schwannoma of histologically benign nature is surgical resection. However, the mass was subtotally resected due to unfavorable intraoperative somatosensory-evoked potential findings, and postoperative fractionated radiotherapy followed. She has been alive with the residual intramedullary mass with no discernible changes during the 11.5 years of follow-up. When neurosurgeons, pediatricians and radiologists encounter an intramedullary tumor in a pediatric patient, intramedullary schwannoma should be included in the differential diagnoses because it might be curable if excised.


Asunto(s)
Imagen por Resonancia Magnética , Neurilemoma/patología , Neurilemoma/cirugía , Neoplasias de la Médula Espinal/patología , Neoplasias de la Médula Espinal/cirugía , Biopsia , Niño , Diagnóstico Diferencial , Femenino , Humanos , Neoplasia Residual/patología , Neurilemoma/radioterapia , Neoplasias de la Médula Espinal/radioterapia , Vértebras Torácicas
12.
Childs Nerv Syst ; 25(1): 29-37, 2009 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-18712399

RESUMEN

OBJECTS: Some basal ganglia germinomas are difficult to diagnose in early stage of disease due to vague initial presentation without discernable mass lesion on brain imaging. We performed this study to determine the usefulness of 11C-methionine positron emission tomography (MET PET) for the diagnosis and monitoring of disease activity. MATERIALS AND METHODS: MET PET was performed in three consecutive patients; they presented with cerebral hemiatrophy without definite mass lesions on brain image. The maximum standard tracer uptake values (max SUVs) were calculated and used for the quantitative evaluation of the abnormal MET uptake. A pathological diagnosis was made after stereotactic biopsy using MET PET/computed tomography. The max SUVs significantly decreased after treatment. CONCLUSION: Basal ganglia germinoma should be considered in the differential diagnosis of patients with progressive hemiparesis and hemiatrophy on magnetic resonance imaging. The MET PET was useful for diagnosis, and it can be valuable in evaluation of treatment effects and monitoring for tumor recurrence.


Asunto(s)
Ganglios Basales/patología , Neoplasias Encefálicas/diagnóstico , Corteza Cerebral/patología , Germinoma/diagnóstico , Adolescente , Atrofia , Neoplasias Encefálicas/etiología , Radioisótopos de Carbono , Niño , Diagnóstico Diferencial , Germinoma/complicaciones , Humanos , Imagen por Resonancia Magnética , Masculino , Metionina , Tomografía de Emisión de Positrones/métodos
13.
J Korean Neurosurg Soc ; 43(6): 265-9, 2008 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-19096630

RESUMEN

OBJECTIVE: Outcome of gamma knife radiosurgery (GKS) in the consecutive 100 cases with cerebral arteriovenous malformations (AVMs) was analyzed. METHODS: Data from initial 100 patients treated with GKS in the authors' institute were reviewed retrospectively. Spetzler-Martin grade at diagnosis were I in 18 patients, II in 27, III in 36, IV in 11, and V in 8. Thirty-five patients had experienced previous bleeding, 27 patients presented with seizure, and 31 patients presented with headache. The mean volume of the lesion was 4.3 cm(3) (0.1-29.3 cm(3)). The median radiation dose delivered to the margin was 20.0 Gy (13-32 Gy). Mean follow-up period was 37.5 months (5-63 months). RESULTS: Angiographic follow-up was performed in 48 patients at least 2 years after GKS. Sixteen patients were lost in follow up following 2 years from GKS. Twenty-eight of 48 patients (58%) showed complete obliteration and 20 patients (42%) showed partial obliteration. Seven patients presented with post-GKS hemorrhage. Adverse radiation effect (ARE) was observed at follow-up MRI in 25 of 76 patients, and it was symptomatic in 5 patients. Complete obliteration was confirmed in 24 of 31 (77%) patients with volume less than 4 cm(3), meanwhile only 4 of 17 (24%) patients with volume of 4 cm(3) or more showed complete obliteration. Complete obliteration rate was 67% with 20 Gy or higher marginal dose, 63% with 15-20 Gy, and 17% with less than 15 Gy. CONCLUSION: GKS can provide high rates of obliteration with acceptable risk of morbidity in a subgroup of small AVMs. However, overall outcome in whole spectrum of AVMs, in which large proportion of cases have unfavorable characteristics for radiosurgery, is much worse. More effective therapeutic strategy needs to be developed for large AVMs that are difficult to be managed with current available treatment modalities.

14.
Korean J Radiol ; 9 Suppl: S26-9, 2008 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-18607121

RESUMEN

We report here on a neonate with congenital cerebellar mixed germ cell tumor, and this initially presented as cerebellar hemorrhage. Postnatal cranial ultrasonography revealed an echogenic cerebellar mass that exhibited the signal characteristics of hemorrhage rather than tumor on MR images. The short-term follow-up images also suggested a resolving cerebellar hemorrhage. One month later, the neonate developed vomiting. A second set of MR images demonstrated an enlarged mass that exhibited changed signal intensity at the same site, which suggested a neoplasm. Histological examination after the surgical resection revealed a mixed germ cell tumor.


Asunto(s)
Enfermedades Cerebelosas/etiología , Neoplasias Cerebelosas/congénito , Hemorragia Cerebral/etiología , Neoplasias de Células Germinales y Embrionarias/congénito , Neoplasias Cerebelosas/diagnóstico , Neoplasias Cerebelosas/diagnóstico por imagen , Femenino , Humanos , Recién Nacido , Imagen por Resonancia Magnética , Neoplasias de Células Germinales y Embrionarias/diagnóstico , Neoplasias de Células Germinales y Embrionarias/diagnóstico por imagen , Ultrasonografía
15.
Oncol Rep ; 16(1): 33-9, 2006 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-16786120

RESUMEN

Glioblastoma is a highly angiogenic tumor with a dismal prognosis. Temozolomide (TMZ), a methylating agent is one of the most effective chemotherapeutic agents against glioblastoma. To overcome the problem that most of these tumors become resistant to chemotherapeutic regimens within a year, we investigated the antitumor efficacy of metronomic administration of low-dose TMZ in in vitro cell proliferation/cytotoxicity assay and in vivo rat and nude mouse orthotopic glioma model. By in vitro assay, we elucidated that C6/LacZ rat glioma cells were more resistant to metronomic treatment of TMZ than U-87MG human glioblastoma cells and bEnd.3 mouse brain endothelial cells. Compared with the conventional chemotherapeutic regimen of TMZ, we found that frequent administration of TMZ at a low dose (metronomic treatment) markedly inhibited angiogenesis as well as tumor growth in a TMZ-resistant C6/LacZ rat glioma model. In addition, metronomic treatment of TMZ significantly augmented apoptosis of tumor cells in this model. For the TMZ-sensitive U-87MG cells, even with a very low dose of TMZ, which is not effective to reduce tumor mass, the metronomic treatment of TMZ reduced the microvessel density, i.e. angiogenesis, in a nude mouse orthotopic model. In conclusion, for both models, the metronomic treatment of TMZ decreased angiogenesis. Especially, in TMZ-resistant glioma cells, this regimen increased apoptosis of tumor cells and decreased tumor growth. The metronomic treatment of TMZ in orthotopic glioma models demonstrated a successful antiangiogenic effect which can overcome the chemoresistance in conventional TMZ chemotherapy.


Asunto(s)
Apoptosis , Dacarbazina/análogos & derivados , Glioma/patología , Neoplasias/tratamiento farmacológico , Neoplasias/metabolismo , Neovascularización Patológica , Animales , Antineoplásicos Alquilantes/farmacología , Línea Celular Tumoral , Dacarbazina/farmacología , Modelos Animales de Enfermedad , Glioma/terapia , Humanos , Masculino , Ratones , Ratones Endogámicos BALB C , Ratas , Ratas Sprague-Dawley , Temozolomida
16.
Childs Nerv Syst ; 21(7): 528-38, 2005 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-15933882

RESUMEN

OBJECTS: Marrow stromal cells (MSCs) have been shown to have the capacity of orthodox and unorthodox plasticity. In this study, the authors tried to access in vitro cytotoxicity of MSCs from rat and also to differentiate MSCs into immune effector cell. METHODS: Rat MSCs (rMSCs) were isolated by standard methodology and were activated by interleukin-2 (IL-2), interleukin-15 (IL-15), granulocyte macrophage colony stimulating factor, and combinations, which were effector cells. Cytotoxicity of rMSCs and activated rMSCs against the target cells (9L rat glioma cell line) was estimated using visual survival cell assay. Phenotypes of these various activated cells were determined using flow cytometry. The secreted protein from effector cells was estimated by enzyme-linked immunosorbent assay. The expression of immune response-related genes in activated cells was measured. RESULTS: There was a significant cytotoxicity of rMSCs activated with various cytokine combinations. After various cytokine activations of rMSCs, the population of immune effector cells (CD8, CD161a) and immune reaction-related proteins (IL-4, gamma-INF) might increase. Apoptosis may be one of the lysis mechanisms of target cells by activated rMSCs. The contributing genes could be gamma-INF, FasL, and perforin. CONCLUSION: This study suggests that rMSC may be used as adoptive transfer therapy in patients suffering from malignant brain tumor, but we have to investigate orthotopic animal study for the proper translation.


Asunto(s)
Células de la Médula Ósea/fisiología , Citocinas/farmacología , Glioma/terapia , Células del Estroma/fisiología , Animales , Antígenos CD/metabolismo , Northern Blotting/métodos , Southern Blotting/métodos , Células de la Médula Ósea/efectos de los fármacos , Recuento de Células/métodos , Supervivencia Celular/fisiología , Células Cultivadas , Técnicas de Cocultivo/métodos , Medios de Cultivo Condicionados/metabolismo , Citocinas/metabolismo , Combinación de Medicamentos , Ensayo de Inmunoadsorción Enzimática/métodos , Proteína Ligando Fas , Citometría de Flujo/métodos , Expresión Génica/efectos de los fármacos , Expresión Génica/fisiología , Proteínas Fluorescentes Verdes/metabolismo , Etiquetado Corte-Fin in Situ/métodos , Interleucina-4/metabolismo , Masculino , Glicoproteínas de Membrana/genética , Glicoproteínas de Membrana/metabolismo , ARN Mensajero/biosíntesis , Ratas , Ratas Sprague-Dawley , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa/métodos , Transfección/métodos , Factores de Necrosis Tumoral/genética , Factores de Necrosis Tumoral/metabolismo
17.
Childs Nerv Syst ; 20(3): 154-62, 2004 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-14968374

RESUMEN

OBJECTS: The aims of this study were to assess the cytotoxic capability of lymphokine-activated killer (LAK) cells from umbilical cord blood (UCB), to compare them with those of peripheral blood (PB)-derived cells against anaplastic astrocytoma cell line (U87) and medulloblastoma cell line (TE671), and to identify which mechanism and genes were involved in cytotoxicity. METHODS: The effector cells were generated by interleukin-2 from UCB and PB. The antitumor property of effector cells against the target cells (U87, TE671) were estimated using a visual survival cell assay. The mixed target and effector (UCB) cells were analyzed for whether DNA fragmentation was present or not. Reverse transcription polymerase chain reaction analysis was then performed to estimate the statement of the perforin and FasL genes in activated and inactivated cells from UCB. RESULTS: The higher in vitro antitumor properties of the LAK cells from UCB were observed in comparison to the LAK cells from PB against the U87 and the TE671 ( p<0.05). Apoptosis may be one of the lysis mechanisms of target cells by the LAK cells from UCB. The contributing genes could be FasL and perforin. CONCLUSIONS: This study suggests that UCB may be used as a source of LAK cells in adults and children suffering from anaplastic astrocytoma or medulloblastoma.


Asunto(s)
Astrocitoma/inmunología , Neoplasias Encefálicas/inmunología , Supervivencia Celular/inmunología , Neoplasias Cerebelosas/inmunología , Sangre Fetal/citología , Células Asesinas Activadas por Linfocinas/inmunología , Linfocitos Infiltrantes de Tumor/inmunología , Meduloblastoma/inmunología , Células Tumorales Cultivadas/inmunología , Adulto , Apoptosis/genética , Apoptosis/inmunología , Astrocitoma/patología , Astrocitoma/terapia , Neoplasias Encefálicas/patología , Neoplasias Encefálicas/terapia , Línea Celular Tumoral , Supervivencia Celular/genética , Neoplasias Cerebelosas/patología , Neoplasias Cerebelosas/terapia , Niño , Pruebas Inmunológicas de Citotoxicidad , Proteína Ligando Fas , Expresión Génica , Humanos , Inmunoterapia Adoptiva , Recién Nacido , Meduloblastoma/patología , Meduloblastoma/terapia , Glicoproteínas de Membrana/genética , Perforina , Proteínas Citotóxicas Formadoras de Poros , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Células Tumorales Cultivadas/patología
18.
Oncol Rep ; 11(2): 263-8, 2004 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-14719052

RESUMEN

Higher cyclooxygenase-2 (COX-2) expression is clinically associated with more aggressive gliomas and is a strong predictor of poor survival. To determine whether oral administration of a COX-2-specific inhibitor can inhibit glial tumors, we analyzed the effect of celecoxib on the growth of 9L rat gliosarcoma cells that were orthotopically transplanted into rat brains. Oral administration of celecoxib beginning 1 day after implantation of 5 x 10(4) 9L rat gliosarcoma cells into rat brain reduced the incidence and size of tumors significantly. Immunohistochemical analysis of implanted gliosarcoma cells from rats treated with celecoxib showed lower levels of phospho-Akt, phospho-EGFR, Bcl-2, and Bcl-XL expression compared with untreated tumor cells. Gliosarcoma cells from treated rats had significantly more TUNEL- and caspase-3-positive cells and fewer PCNA-positive cells. These results demonstrate that selective COX-2 inhibitors may be useful as adjuvants and/or therapeutic agents to treat gliomas overexpressing COX-2.


Asunto(s)
Antineoplásicos/toxicidad , Neoplasias Encefálicas/patología , Encéfalo/patología , Glioma/patología , Sulfonamidas/toxicidad , Animales , Apoptosis/efectos de los fármacos , Celecoxib , División Celular/efectos de los fármacos , Inhibidores de la Ciclooxigenasa/toxicidad , Gliosarcoma , Etiquetado Corte-Fin in Situ , Masculino , Antígeno Nuclear de Célula en Proliferación/análisis , Pirazoles , Ratas , Ratas Sprague-Dawley
19.
Pediatr Radiol ; 33(12): 836-42, 2003 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-14564423

RESUMEN

BACKGROUND: Glioblastoma is relatively uncommon in childhood and maybe difficult to differentiate from other brain tumors such as primitive neuroectodermal tumor, ependymoma, or benign astrocytoma. OBJECTIVE: To describe the characteristic MR features in children with glioblastoma and to evaluate the usefulness of diffusion and perfusion MR imaging and MR spectroscopy in pediatric glioblastoma. MATERIALS AND METHODS: MR imaging in 11 children (12 tumors) with biopsy-proven glioblastoma was reviewed retrospectively. In one patient, there was a recurrent glioblastoma. We reviewed CT and MRI imaging for tumor location, density/signal intensity, and enhancement pattern. Routine MR imaging was performed with a 1.5-T scanner. In six patients, diffusion-weighted MR images (DWIs) were obtained with a single-shot spin echo EPI technique with two gradient steps, and apparent diffusion coefficients (ADCs) were calculated. Using the gradient EPI technique, perfusion-weighted MR images (PWIs) were obtained in four patients from the data of dynamic MR images. The maximum relative cerebral blood volume (rCBV) ratio was calculated between the tumor and contralateral white matter in two cases. In three patients, proton MR spectroscopy was performed using a single voxel technique with either STEAM or PRESS sequences. The locations of the tumor were the thalamus and basal ganglia ( n=8), deep white matter ( n=3), and brain stem ( n=1). RESULTS: Intratumoral hemorrhage was seen in four tumors. The tumors showed high-signal intensity or DWIs, having a wide range of ADC values of 0.53-1.30 (mean +/-SD=1.011+/-0.29). The maximum rCBV ratios of glioblastoma were 10.2 and 8.5 in two cases. MR spectroscopy showed decreased N-acetylaspartate (NAA) and increased choline in three cases. The MR findings of glioblastoma in children were: a diffusely infiltrative mass with hemorrhage involving the deep cerebral white matter, thalami, and basal ganglia. CONCLUSION: Diffusion/perfusion MR imaging and MR spectroscopy are very helpful in diagnosing glioblastoma, determining the biopsy site, and evaluating tumor recurrence.


Asunto(s)
Neoplasias Encefálicas/diagnóstico , Glioblastoma/diagnóstico , Imagen por Resonancia Magnética/métodos , Adolescente , Neoplasias Encefálicas/patología , Niño , Preescolar , Femenino , Glioblastoma/patología , Humanos , Lactante , Masculino , Estudios Retrospectivos
20.
J Clin Neurosci ; 10(4): 439-43, 2003 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-12852882

RESUMEN

We reviewed 63 patients with primary intracerebral haemorrhage (PICH) in basal ganglia treated by computed tomography (CT)-guided stereotactic aspiration to evaluate the impact of surgical timing and degree of haematoma volume reduction on neurological outcome evaluated with Glasgow Outcome Score (GOS). In 19 patients operation was performed within 24h from the symptom onset with more than 60% of haematoma volume reduction. At 3 weeks 11 patients (58%) achieved a favorable outcome (GOS 4 or 5). In the other 44 patients only 10 (23%) recovered to GOS 4 or 5. These differences were statistically significant. At 6 months a still larger proportion of patients with early radical decompression showed favorable outcome, however, the difference was not statistically significant. The results demonstrate that early and radical stereotactic aspiration provided a better neurological outcome at the early recovery phase, though the beneficial effect on the final outcome was not significant statistically.


Asunto(s)
Hemorragia Cerebral/cirugía , Hematoma Epidural Craneal/cirugía , Adulto , Anciano , Ganglios Basales/patología , Hemorragia Cerebral/diagnóstico por imagen , Hemorragia Cerebral/patología , Descompresión Quirúrgica/efectos adversos , Descompresión Quirúrgica/métodos , Femenino , Lateralidad Funcional , Hematoma Epidural Craneal/diagnóstico por imagen , Hematoma Epidural Craneal/patología , Humanos , Masculino , Persona de Mediana Edad , Periodo Posoperatorio , Estudios Retrospectivos , Técnicas Estereotáxicas/efectos adversos , Terapia Trombolítica/métodos , Tomografía Computarizada por Rayos X , Resultado del Tratamiento
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