RESUMEN
Neurodevelopmental disorder with microcephaly, hypotonia, and variable brain anomalies (NMIHBA) (OMIM #617481) is an autosomal recessive disease characterized by progressive microcephaly, plagiocephaly, hypotonia, spastic quadriparesis, global developmental delay, intellectual disability, optic features and abnormal brain magnetic resonance imaging (MRI). NMIHBA was recently reported to be caused by PRUNE1 mutations. Eight mutations have been reported in 13 unrelated families. Here, we report 3 PRUNE1 mutations in 1 Caucasian and 3 Japanese families. One recurrent missense mutation (p.Asp106Asn) was previously reported in Turkish and Italian families, while the other 2 mutations (p.Leu18Serfs*8 and p.Cys180*) are novel. We also show that mutant PRUNE1 mRNA can be subject to nonsense-mediated mRNA decay. The patients presented in this study showed atypical NMIHBA phenotypes with no progressive microcephaly. Furthermore, one Caucasian case had significant macrocephaly; therefore, patients with PRUNE1 mutations can exhibit a broad and heterogeneous spectrum of phenotypes.
Asunto(s)
Encéfalo/anomalías , Microcefalia/genética , Hipotonía Muscular/genética , Monoéster Fosfórico Hidrolasas/genética , Encéfalo/diagnóstico por imagen , Niño , Femenino , Humanos , Italia , Imagen por Resonancia Magnética , Masculino , Mutación Missense , Linaje , ARN Mensajero/genética , TurquíaAsunto(s)
Neuropatía Hereditaria Motora y Sensorial/genética , Atrofia Muscular Espinal/genética , Simportadores/genética , Femenino , Neuropatía Hereditaria Motora y Sensorial/fisiopatología , Humanos , Japón , Mutación con Pérdida de Función/genética , Masculino , Persona de Mediana Edad , Atrofia Muscular Espinal/fisiopatología , Linaje , GalesRESUMEN
Leukoencephalopathies encompass all clinical syndromes that predominantly affect brain white matter. Genetic diagnosis informs clinical management of these patients, but a large part of the genetic contribution to adult leukoencephalopathy remains unresolved. To examine this genetic contribution, we analyzed genomic DNA from 60 Japanese patients with adult leukoencephalopathy of unknown cause by next generation sequencing using a custom-designed gene panel. We selected 55 leukoencephalopathy-related genes for the gene panel. We identified pathogenic mutations in 8 of the 60 adult leukoencephalopathy patients (13.3%): NOTCH3 mutations were detected in 5 patients, and EIF2B2, CSF1R, and POLR3A mutations were found independently in 1 patient each. These results indicate that cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) caused by NOTCH3 mutations is the most frequent adult leukoencephalopathy in our cohort. Moreover, brain imaging analysis indicates that CADASIL patients who do not present typical phenotypes may be underdiagnosed if not examined genetically.
Asunto(s)
CADASIL/genética , Predisposición Genética a la Enfermedad , Leucoencefalopatías/genética , Receptor Notch3/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , CADASIL/diagnóstico por imagen , CADASIL/fisiopatología , Estudios de Cohortes , Factor 2B Eucariótico de Iniciación/genética , Pruebas Genéticas , Humanos , Leucoencefalopatías/diagnóstico por imagen , Leucoencefalopatías/fisiopatología , Imagen por Resonancia Magnética , Persona de Mediana Edad , Mutación , Fenotipo , ARN Polimerasa III/genética , Receptores de Factor Estimulante de Colonias de Granulocitos y Macrófagos/genética , Secuenciación del ExomaRESUMEN
A novel causative variant (c.608G>A, p.Arg203Gln) in PACS1.
Asunto(s)
Secuencia de Aminoácidos/genética , Discapacidades del Desarrollo/genética , Exoma/genética , Proteínas de Transporte Vesicular/genética , Preescolar , Discapacidades del Desarrollo/fisiopatología , Femenino , Humanos , Masculino , FenotipoRESUMEN
Epilepsies are common neurological disorders and genetic factors contribute to their pathogenesis. Copy number variations (CNVs) are increasingly recognized as an important etiology of many human diseases including epilepsy. Whole-exome sequencing (WES) is becoming a standard tool for detecting pathogenic mutations and has recently been applied to detecting CNVs. Here, we analyzed 294 families with epilepsy using WES, and focused on 168 families with no causative single nucleotide variants in known epilepsy-associated genes to further validate CNVs using 2 different CNV detection tools using WES data. We confirmed 18 pathogenic CNVs, and 2 deletions and 2 duplications at chr15q11.2 of clinically unknown significance. Of note, we were able to identify small CNVs less than 10 kb in size, which might be difficult to detect by conventional microarray. We revealed 2 cases with pathogenic CNVs that one of the 2 CNV detection tools failed to find, suggesting that using different CNV tools is recommended to increase diagnostic yield. Considering a relatively high discovery rate of CNVs (18 out of 168 families, 10.7%) and successful detection of CNV with <10 kb in size, CNV detection by WES may be able to surrogate, or at least complement, conventional microarray analysis.
Asunto(s)
Variaciones en el Número de Copia de ADN , Epilepsia/genética , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Pruebas Genéticas , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Alelos , Niño , Preescolar , Hibridación Genómica Comparativa , Biología Computacional/métodos , Epilepsia/diagnóstico , Exoma , Femenino , Estudios de Asociación Genética/métodos , Pruebas Genéticas/métodos , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Masculino , Persona de Mediana Edad , Mutación , Secuenciación del Exoma , Adulto JovenRESUMEN
The seizure threshold 2 (SZT2) gene encodes a large, highly conserved protein that is associated with epileptogenesis. In mice, Szt2 is abundantly expressed in the central nervous system. Recently, biallelic SZT2 mutations were found in 7 patients (from 5 families) presenting with epileptic encephalopathy with dysmorphic features and/or non-syndromic intellectual disabilities. In this study, we identified by whole-exome sequencing compound heterozygous SZT2 mutations in 3 patients with early-onset epileptic encephalopathies. Six novel SZT2 mutations were found, including 3 truncating, 1 splice site and 2 missense mutations. The splice-site mutation resulted in skipping of exon 20 and was associated with a premature stop codon. All individuals presented with seizures, severe developmental delay and intellectual disabilities with high variability. Brain MRIs revealed a characteristic thick and short corpus callosum or a persistent cavum septum pellucidum in each of the 2 cases. Interestingly, in the third case, born to consanguineous parents, had unexpected compound heterozygous missense mutations. She showed microcephaly despite the other case and previous ones presenting with macrocephaly, suggesting that SZT2 mutations might affect head size.
Asunto(s)
Epilepsia Generalizada/genética , Discapacidad Intelectual/genética , Proteínas del Tejido Nervioso/genética , Espasmos Infantiles/genética , Preescolar , Epilepsia Generalizada/diagnóstico por imagen , Epilepsia Generalizada/patología , Femenino , Humanos , Lactante , Discapacidad Intelectual/diagnóstico por imagen , Discapacidad Intelectual/patología , Imagen por Resonancia Magnética , Masculino , Mutación Missense/genética , Linaje , Sitios de Empalme de ARN/genética , Espasmos Infantiles/diagnóstico por imagen , Espasmos Infantiles/patología , Secuenciación del ExomaRESUMEN
A novel causative variant (c. 464T>C, p.Leu155Pro) in the heterogeneous nuclear ribonucleoprotein K (HNRNPK) gene.
Asunto(s)
Anomalías Múltiples/genética , Cara/anomalías , Enfermedades Hematológicas/genética , Ribonucleoproteína Heterogénea-Nuclear Grupo K/genética , Mutación Missense/genética , Enfermedades Vestibulares/genética , Secuencia de Aminoácidos , Secuencia de Bases , Preescolar , Ribonucleoproteína Heterogénea-Nuclear Grupo K/química , Humanos , MasculinoRESUMEN
Genetic reversion is the phenomenon of spontaneous gene correction by which gene function is partially or completely rescued. However, it is unknown whether this mechanism always correctly repairs mutations, or is prone to error. We investigated a family of three boys with intellectual disability, and among them we identified two different mutations in KDM5C, located at Xp11.22, using whole-exome sequencing. Two affected boys have c.633delG and the other has c.631delC. We also confirmed de novo germline (c.631delC) and low-prevalence somatic (c.633delG) mutations in their mother. The two mutations are present on the same maternal haplotype, suggesting that a postzygotic somatic mutation or a reversion error occurred at an early embryonic stage in the mother, leading to switched KDM5C mutations in the affected siblings. This event is extremely unlikely to arise spontaneously (with an estimated probability of 0.39-7.5 × 10(-28) ), thus a possible reversion error is proposed here to explain this event. This study provides evidence for reversion error as a novel mechanism for the generation of somatic mutations in human diseases.
Asunto(s)
Histona Demetilasas/genética , Discapacidad Intelectual/genética , Herencia Materna/genética , Mutación/genética , Preescolar , Exoma , Femenino , Genes Ligados a X , Haplotipos , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Lactante , Discapacidad Intelectual/fisiopatología , Masculino , Mosaicismo , Madres , Linaje , FenotipoAsunto(s)
Proteínas del Citoesqueleto/genética , Neuropatía Axonal Gigante/genética , Neuropatía Axonal Gigante/patología , Disomía Uniparental/genética , Secuencia de Bases , Exoma/genética , Femenino , Homocigoto , Humanos , Imagen por Resonancia Magnética , Datos de Secuencia Molecular , Conducción Nerviosa/genética , Conducción Nerviosa/fisiología , Análisis de Secuencia de ADNRESUMEN
OBJECTIVE: RNF213 was recently reported as a susceptibility gene for moyamoya disease (MMD). Our aim was to clarify the correlation between the RNF213 genotype and MMD phenotype. METHODS: The entire coding region of the RNF213 gene was sequenced in 204 patients with MMD, and corresponding variants were checked in 62 pairs of parents, 13 mothers and 4 fathers of the patients, and 283 normal controls. Clinical information was collected. Genotype-phenotype correlations were statistically analyzed. RESULTS: The c.14576G>A variant was identified in 95.1% of patients with familial MMD, 79.2% of patients with sporadic MMD, and 1.8% of controls, thus confirming its association with MMD, with an odds ratio of 259 and p < 0.001 for either heterozygotes or homozygotes. Homozygous c.14576G>A was observed in 15 patients but not in the controls and unaffected parents. The incidence rate for homozygotes was calculated to be >78%. Homozygotes had a significantly earlier age at onset compared with heterozygotes or wild types (median age at onset 3, 7, and 8 years, respectively). Of homozygotes, 60% were diagnosed with MMD before age 4, and all had infarctions as the first symptom. Infarctions at initial presentation and involvement of posterior cerebral arteries, both known as poor prognostic factors for MMD, were of significantly higher frequency in homozygotes than in heterozygotes and wild types. Variants other than c.14576G>A were not associated with clinical phenotypes. CONCLUSIONS: The homozygous c.14576G>A variant in RNF213 could be a good DNA biomarker for predicting the severe type of MMD, for which early medical/surgical intervention is recommended, and may provide a better monitoring and prevention strategy.
Asunto(s)
Enfermedad de Moyamoya/genética , Ubiquitina-Proteína Ligasas/genética , Adenosina Trifosfatasas , Adolescente , Adulto , Edad de Inicio , Biomarcadores , Infarto Cerebral/etiología , Niño , Preescolar , ADN/genética , Análisis Mutacional de ADN , Epilepsia/complicaciones , Familia , Femenino , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Variación Genética , Genotipo , Homocigoto , Humanos , Lactante , Recién Nacido , Discapacidad Intelectual/complicaciones , Discapacidad Intelectual/psicología , Masculino , Persona de Mediana Edad , Enfermedad de Moyamoya/patología , Fenotipo , Arteria Cerebral Posterior/patología , Valor Predictivo de las Pruebas , Caracteres Sexuales , Adulto JovenAsunto(s)
Aspartato-ARNt Ligasa/genética , Trastornos de los Cromosomas , Cromosomas Humanos Par 1 , Ácido Láctico/metabolismo , Mitocondrias/genética , Síndrome de Leucoencefalopatía Posterior/genética , Edad de Inicio , Preescolar , Consanguinidad , Análisis Mutacional de ADN , Femenino , Genes Recesivos , Ligamiento Genético , Haplotipos , Homocigoto , Humanos , Japón , Espectroscopía de Resonancia Magnética , Masculino , Mitocondrias/metabolismo , Mutación , Síndrome de Leucoencefalopatía Posterior/patologíaRESUMEN
Hepatocyte growth factor (HGF) promotes regeneration of the central nervous system, but its effects on the peripheral nervous system remain unclear. This study was conducted to elucidate the effect of HGF on regeneration of the murine facial nerve after crush injury. To do so, a replication-defective herpes simplex virus vector that incorporated HGF was prepared (HSV-HGF). The main trunk of the facial nerve was compressed by mosquito hemostats, and HSV-HGF, control vector or medium was then applied to the compressed nerve. We found that mice in the HGF group required significantly fewer days for complete recovery from nerve compression. Furthermore, the amplitude of the evoked buccinator muscle compound action potential increased following HSV-HGF application. HGF expression in and around the compressed nerve was demonstrated by enzyme-linked immunoassay and immunohistochemistry. In addition, HSV-HGF introduction around the damaged nerve significantly accelerated recovery of function of the facial nerve. These data suggest a possible role of HGF in promoting facial nerve regeneration after nerve damage. Furthermore, this viral delivery method may be applied clinically for many types of severe facial palsy during facial nerve decompression surgery.
Asunto(s)
Traumatismos del Nervio Facial/terapia , Terapia Genética/métodos , Factor de Crecimiento de Hepatocito/genética , Regeneración Nerviosa/efectos de los fármacos , Simplexvirus/genética , Animales , Nervio Facial/fisiología , Vectores Genéticos , Ratones , Síndromes de Compresión Nerviosa/terapia , Regeneración Nerviosa/genéticaRESUMEN
Clear cell sarcoma (CCS) is a rare melanocytic malignant tumor with a poor prognosis. Our previous study demonstrated that in vitro cultured CCS cells have the ability to highly uptake l-BPA and thus boron neutron capture therapy could be a new option for CCS treatment. This paper proved that a remarkably high accumulation of (10)B (45-74 ppm) in tumor was obtained even in a CCS-bearing animal with a well-controlled biodistribution followed by intravenous administration of L-BPA-fructose complex (500 mg BPA/kg).
Asunto(s)
Compuestos de Boro/farmacocinética , Terapia por Captura de Neutrón de Boro , Fenilalanina/análogos & derivados , Sarcoma de Células Claras/radioterapia , Adolescente , Animales , Línea Celular Tumoral , Femenino , Humanos , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Fenilalanina/farmacocinética , Sarcoma de Células Claras/metabolismo , Distribución TisularRESUMEN
BNCT requires high concentration and selective delivery of (10)B to the tumor cell. To improve the drug delivery in BNCT, we conducted a study by devising TPLB. We administrated three types of boron delivery systems: BSH, PLB and TPLB, to Oral SCC bearing mice. Results confirmed that (10)B concentration is higher in the TPLB group than in the BSH group and that TPLB is significantly effective as boron delivery system.
Asunto(s)
Borohidruros/administración & dosificación , Borohidruros/farmacocinética , Terapia por Captura de Neutrón de Boro/métodos , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/radioterapia , Neoplasias de la Boca/metabolismo , Neoplasias de la Boca/radioterapia , Fármacos Sensibilizantes a Radiaciones/administración & dosificación , Fármacos Sensibilizantes a Radiaciones/farmacocinética , Compuestos de Sulfhidrilo/administración & dosificación , Compuestos de Sulfhidrilo/farmacocinética , Animales , Borohidruros/uso terapéutico , Línea Celular Tumoral , Sistemas de Liberación de Medicamentos , Liposomas , Masculino , Ratones , Ratones Endogámicos BALB C , Polietilenglicoles , Fármacos Sensibilizantes a Radiaciones/uso terapéutico , Compuestos de Sulfhidrilo/uso terapéutico , TransferrinaRESUMEN
We treated 6 patients with recurrent oral cancer and metastasis to the cervical lymph nodes after conventional treatments in 5 and non-conventional in 1 using BNCT, and herein report our results. The clinical response in our patients ranged from CR to PD. In 5 cases, spontaneous pain decreased immediately after BNCT. Three of the 6 are alive at the time of writing and we found that BNCT contributed to QOL improvement in all.
Asunto(s)
Terapia por Captura de Neutrón de Boro , Metástasis Linfática/radioterapia , Neoplasias de la Boca/radioterapia , Recurrencia Local de Neoplasia/radioterapia , Adulto , Anciano , Anciano de 80 o más Años , Compuestos de Boro/uso terapéutico , Femenino , Radioisótopos de Flúor , Humanos , Metástasis Linfática/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Neoplasias de la Boca/diagnóstico por imagen , Neoplasias de la Boca/fisiopatología , Cuello , Recurrencia Local de Neoplasia/diagnóstico por imagen , Recurrencia Local de Neoplasia/fisiopatología , Dolor/fisiopatología , Fenilalanina/análogos & derivados , Fenilalanina/uso terapéutico , Tomografía de Emisión de Positrones , Calidad de Vida , Fármacos Sensibilizantes a Radiaciones/uso terapéutico , Radiofármacos , Tomografía Computarizada por Rayos XRESUMEN
Boron neutron capture therapy (BNCT) is a tumor-selective radiation therapy using alpha and (7)Li particles, which are produced by the reaction of neutron with boron ((10)B), and taken up by the tumor. The authors report their first experience of BNCT on a patient with no history of surgery, chemotherapy or conventional radiotherapy for papillary cystadenocarcinoma in the upper lip.
Asunto(s)
Terapia por Captura de Neutrón de Boro/métodos , Cistadenocarcinoma Papilar/radioterapia , Neoplasias de los Labios/radioterapia , Anciano , Cistadenocarcinoma Papilar/patología , Femenino , Humanos , Neoplasias de los Labios/patología , Imagen por Resonancia Magnética , Dosis de Radiación , Resultado del TratamientoRESUMEN
Radiation-induced cavernous malformations are rarely reported, and most cases have been children. We describe two adult patients with cavernous malformation after irradiation for astrocytoma. Magnetic resonance (MR) imaging, at their ages of 53 years, showed a cavernous malformation in the irradiated field 26 and 10 years after resection and irradiation, respectively. Cavernous malformations were confirmed by the histopathological examination in the both cases. Radiation-induced cavernous malformations are rare in adult patients with astrocytoma. One reason why we found two such cases was that these patients had been successfully treated for astrocytoma and had long follow-up periods.
Asunto(s)
Astrocitoma/radioterapia , Vasos Sanguíneos/patología , Vasos Sanguíneos/efectos de la radiación , Neoplasias Encefálicas/radioterapia , Hemangioma Cavernoso del Sistema Nervioso Central/etiología , Neoplasias Inducidas por Radiación/etiología , Radioterapia/efectos adversos , Astrocitoma/diagnóstico , Vasos Sanguíneos/fisiopatología , Neoplasias Encefálicas/diagnóstico , Neoplasias Cerebelosas/diagnóstico , Neoplasias Cerebelosas/radioterapia , Demencia/diagnóstico , Demencia/etiología , Demencia/fisiopatología , Lóbulo Frontal/irrigación sanguínea , Lóbulo Frontal/patología , Lóbulo Frontal/efectos de la radiación , Hemangioma Cavernoso del Sistema Nervioso Central/diagnóstico , Hemangioma Cavernoso del Sistema Nervioso Central/fisiopatología , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Neoplasias Inducidas por Radiación/diagnóstico , Neoplasias Inducidas por Radiación/fisiopatología , Lóbulo Temporal/irrigación sanguínea , Lóbulo Temporal/patología , Lóbulo Temporal/efectos de la radiación , Tomografía Computarizada por Rayos XRESUMEN
In this study, brain functions in stroke patients and normal subjects were analyzed by observing neuromagnetic fields during button pressing tasks. The measurements included force measurement, visual stimuli presentation and magnetoencephalography (MEG). A 122-channel whole-head MEG system (Neuromag 122) was used. A total of 18 subjects (11 post-stroke and 7 control subjects) participated in the study; adequate MEG data were obtained from 3 of the patients. Equivalent current dipoles for MRFs were estimated with the following parameters: goodness of fit (> 75%), confidence volume (< 6000 mm3), and the duration of dipole (> 10 msec). In addition to the single dipole analysis, Minimum Current Estimates were applied for source estimation since neural activities for stroke patients were observed at the motor cortex of the contralateral side as well as other areas of the brain. Contralateral motor cortex was activated for the normal subjects at 50 ms prior to the force onset, whereas ipsilateral motor cortex was activated for some stroke patients and patients' dipole moments differed not only in their locations but also in their latencies, ranging from -150 to 50 ms to the force onset. The results were in agreement with the findings by PET and fMRI studies; therefore, it was implied that the compensating motor functions were shifted to neighboring areas of the brain due to the recovering motor function after stroke.
Asunto(s)
Potenciales Evocados Motores/fisiología , Magnetoencefalografía/métodos , Movimiento/fisiología , Desempeño Psicomotor/fisiología , Accidente Cerebrovascular/fisiopatología , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Corteza Motora/fisiología , Accidente Cerebrovascular/diagnóstico , Factores de TiempoRESUMEN
We previously reported adenovirus-mediated ex vivo gene transfer of basic fibroblast growth factor (bFGF) as a new treatment for leg ischemia. This time, we tested this method on a swine myocardial ischemia model, seeking the possibility of its application for ischemic heart disease. An ameroid constrictor was placed around the proximal left circumflex branch of pigs to induce myocardial ischemia. Simultaneously, a skin section was harvested and fibroblasts were cultured. Fibroblasts were then infected with adenovirus vector containing a bFGF cDNA with a secretory signal sequence (bFGF group, n=8) or a LacZ cDNA (control group, n=8). At 28 days after constrictor implantation, 2.5 x 10(6) fibroblasts were administered into each of the right and left coronary arteries. The injected fibroblasts accumulated in the myocardium without causing myocardial ischemia. Echocardiography, electromechanical mapping and coronary arteriography were conducted just before and 28 days after fibroblast injection, and regional left ventricular myocardial blood flow was measured 28 days after fibroblast injection. These evaluations revealed that the bFGF group exhibited significant development of collateral vessels and improvement of myocardial contraction in the ischemic area compared with the control group. We believe that this method is a promising treatment strategy for ischemic heart disease.
Asunto(s)
Factor 2 de Crecimiento de Fibroblastos/genética , Fibroblastos/metabolismo , Terapia Genética/métodos , Isquemia Miocárdica/terapia , Miocardio/metabolismo , Transducción Genética/métodos , Adenoviridae/genética , Animales , Western Blotting , Trasplante de Células/métodos , Circulación Colateral , Angiografía Coronaria , Vasos Coronarios , Ecocardiografía , Factor 2 de Crecimiento de Fibroblastos/análisis , Factor 2 de Crecimiento de Fibroblastos/metabolismo , Vectores Genéticos/administración & dosificación , Inyecciones Intravenosas , Masculino , Modelos Animales , Contracción Miocárdica , Isquemia Miocárdica/metabolismo , Isquemia Miocárdica/fisiopatología , PorcinosRESUMEN
Takagaki, M., Ono, K., Masunaga, S-I., Kinashi, Y., Oda, Y., Miyatake, S-I., Hashimoto, N., Powell, W., Sood, A. and Spielvogel, B. F. Boronated Dipeptide Borotrimethylglycylphenylalanine as a Potential Boron Carrier in Boron Neutron Capture Therapy for Malignant Brain Tumors. Radiat. Res. 156, 118-122 (2001).A boronated dipeptide, borotrimethylglycylphenylalanine (BGPA), was synthesized as a possible boron carrier for boron neutron capture therapy (BNCT) for malignant brain tumors. In vitro, at equal concentrations of (10)B in the extracellular medium, BGPA had the same effect in BNCT as p-boronophenylalanine (BPA). Boron analysis was carried out using prompt gamma-ray spectrometry and track-etch autoradiography. The tumor:blood and tumor:normal brain (10)B concentration ratios were 8.9 +/- 2.1 and 3.0 +/- 1.2, respectively, in rats bearing intracranial C6 gliosarcomas using alpha-particle track autoradiography. The IC(50), i.e. the dose capable of inhibiting the growth of C6 gliosarcoma cells by 50% after 3 days of incubation, was 5.9 x 10(-3) M BGPA, which is similar to that of 6.4 x 10(-3) M for BPA. The amide bond of BGPA is free from enzymatic attack, since it is protected from hydrolysis by the presence of a boron atom at the alpha-carbon position of glycine. These results suggest promise for the use of this agent for BNCT of malignant brain tumors. Further preclinical studies of BGPA are warranted, since BGPA has advantages over both BPA and BSH.