RESUMO
The fruit neck is an important agronomic trait of cucumber (Cucumis sativus). However, the underlying genes and regulatory mechanisms involved in fruit neck development are poorly understood. We previously identified a cucumber yellow-green peel (ygp) mutant, whose causal gene is MYB DOMAIN PROTEIN 36 (CsMYB36). This study showed that the ygp mutant exhibited a shortened fruit neck and repressed cell expansion in the fruit neck. Further functional analysis showed that CsMYB36 was also a target gene, and its expression was enriched in the fruit neck. Overexpression of CsMYB36 in the ygp mutant rescued shortened fruit necks. Furthermore, transcriptome analysis and reverse transcription quantitative PCR (RT-qPCR) assays revealed that CsMYB36 positively regulates the expression of an expansin-like A3 (CsEXLA3) in the fruit neck, which is essential for cell expansion. Yeast 1-hybrid and dual-luciferase assays revealed that CsMYB36 regulates fruit neck elongation by directly binding to the promoter of CsEXLA3. Collectively, these findings demonstrate that CsMYB36 is an important gene in the regulation of fruit neck length in cucumber plants.
Assuntos
Cucumis sativus , Frutas , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas , Fatores de Transcrição , Cucumis sativus/genética , Cucumis sativus/crescimento & desenvolvimento , Frutas/genética , Frutas/crescimento & desenvolvimento , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genéticaRESUMO
Increased planting densities boost crop yields. A compact plant architecture facilitates dense planting. However, the mechanisms regulating compact plant architecture in cucurbits remain unclear. In this study, we identified a cucumber (Cucumis sativus) compact plant architecture (cpa1) mutant from an ethyl methane sulfonate (EMS)-mutagenized library that exhibited distinctive phenotypic traits, including reduced leaf petiole angle and leaf size. The candidate mutation causes a premature stop codon in CsaV3_1G036420, which shares similarity to Arabidopsis HOOKLESS 1 (HLS1) encoding putative histone N-acetyltransferase (HAT) protein and was named CsHLS1. Consistent with the mutant phenotype, CsHLS1 was predominantly expressed in leaf petiole bases and leaves. Constitutive overexpressing CsHLS1 in cpa1 restored the wild-type plant architecture. Knockout of CsHLS1 resulted in reduces leaf petiole angle and leaf size and as well as decreased acetylation levels. Furthermore, CsHLS1 directly interacted with CsSCL28 and negatively regulated compact plant architecture in cucumber. Importantly, CsHLS1 knockout increased the photosynthesis rate and leaf nitrogen in cucumbers, thereby maintaining cucumber yield at normal density. Overall, our research provides valuable genetic breeding resource and gene target for creating a compact plant architecture for dense cucumber planting.
Assuntos
Cucumis sativus , Folhas de Planta , Proteínas de Plantas , Cucumis sativus/genética , Cucumis sativus/crescimento & desenvolvimento , Cucumis sativus/anatomia & histologia , Cucumis sativus/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Folhas de Planta/genética , Folhas de Planta/crescimento & desenvolvimento , Folhas de Planta/anatomia & histologia , Folhas de Planta/metabolismo , Regulação da Expressão Gênica de Plantas , Fotossíntese/genética , Mutação , Histona Acetiltransferases/genética , Histona Acetiltransferases/metabolismoRESUMO
Copolymerization of elemental sulfur (S8) with vinyl monomers to develop new polymer materials is significant. Here, for the first time, we report the anionic hybrid copolymerization of S8 with acrylate at 25 °C, yielding a copolymer with short polysulfide segments; i.e., each of them consists of only one to four sulfur atoms. The formation of a longer polysulfide segment would be ceaselessly disrupted by carbon anions through the chain-transfer reaction. The copolymer of S8 with diacrylate was cross-linked and exhibited excellent mechanical properties, with an ultimate tensile strength as high as 10.7 MPa and a breaking strain of 22%. Furthermore, the introduction of tertiary amide groups to the copolymer enabled it not only to be reprocessed via press molding at room temperature but also to exhibit self-healing properties without external intervention. This study provides a facile strategy to synthesize high-performance sulfur-based copolymers under mild conditions.
RESUMO
OBJECTIVE: To investigate the factors affecting phenotypes in the patients of methylmalonic acidemia combined with homocysteinemia cblC type with MMACHC c.609G>A homologous variant. METHODS: A retrospective study on the clinical manifestations, complications, treatment, and outcome in 164 patients of cblC type with MMACHC c.609G>A homologous variant was conducted. The patients were diagnosed by biochemical and genetic analysis from January 1998 to December 2020. RESULTS: Among the 164 patients, 2 cases were prenatally diagnosed and began treatment after birth. They are 3 and 12 years old with normal physical and mental development. Twenty-one cases were diagnosed by newborn screening. Among them, 15 cases had with normal development. They were treated from the age of two weeks at the asymptomatic period. Six cases began treatment aged 1 to 3 months after onset. Their development was delayed. One hundred and forty-one cases were clinically diagnosed. Their onset age ranges from a few minutes after birth to 6 years old. 110 cases had early-onset (78.0%). 31 cases had late-onset (22.0%). Five of them died. 24 patients lost to follow-up. Of the 141 clinically diagnosed patients, 130 (92.2%) with psychomotor retardation, 69 (48.9%) with epilepsy, 39 (27.7%) with anemia, 30 (21.3%) had visual impairment, 27 (19.1%) had hydrocephalus, 26 (18.4%) had feeding difficulties, 7 (5.0%) with liver damage, and 5 (3.5%) with metabolic syndrome. The frequency of hydrocephalus and seizures was significantly higher in the early-onset group. The urinary methylmalonic acid increased significantly in the patients with epilepsy. During the long-term follow-up, the level of plasma total homocysteine in the seizure-uncontrolled group was significantly higher than that in the seizure-controlled group, the difference had a statistical significance (P<0.05). CONCLUSION: Most of the patients with MMACHC c.609G>A homozygous variant had early-onset disease, with a high mortality and disability rate. If not treated in time, it will lead to neurological damage, resulting in epilepsy, mental retardation, hydrocephalus, and multiple organ damage. Pre-symptomatic diagnosis and treatment are crucial to prevent irreversible neurological damage. Neonatal screening and prenatal diagnosis are important to improve the outcome of the patients.
Assuntos
Erros Inatos do Metabolismo dos Aminoácidos , Hidrocefalia , Oxirredutases , Erros Inatos do Metabolismo dos Aminoácidos/diagnóstico , Erros Inatos do Metabolismo dos Aminoácidos/enzimologia , Erros Inatos do Metabolismo dos Aminoácidos/genética , Feminino , Humanos , Hidrocefalia/diagnóstico , Hidrocefalia/enzimologia , Hidrocefalia/genética , Mutação , Oxirredutases/genética , Fenótipo , Gravidez , Estudos Retrospectivos , Convulsões/genéticaRESUMO
BACKGROUND: Monohydroxycarbamazepine (MHD, 10-hydroxy-carbamazepine) is the main active metabolite of oxcarbazepine (OXC). The present study aims to investigate the relationship between plasma and saliva concentrations of MHD in Chinese children with epilepsy. METHODS: Plasma and saliva samples were collected and MHD levels were measured by high-performance liquid chromatography system. Linear regression analysis was conducted between the dose of OXC and saliva concentrations, between the dose of OXC and plasma concentrations, and between the saliva concentrations and plasma concentrations. Student's t-test was used for unpaired data. A one-way analysis of variance was used for analyzing co-medication in subgroups of patients. RESULTS: A total of 58 blood samples and 58 saliva samples were obtained from 52 pediatric epileptic patients, with a median age of 5.67 years (0.58-15 years, 23 males and 29 females). There was an apparent positive correlation between the plasma and saliva MHD concentrations [Y = 0.77x - 0.85 (n = 58), R = 0.908, P < 0.01]. MHD plasma and saliva concentrations were positively correlated to daily drug dose (r = 0.461 and 0.417; P < 0.01 respectively). The saliva/plasma MHD ratio was around 0.71 and had no significant difference with age, gender, and combined medications. When data were analyzed for subgroups (one group taking OXC as monotherapy, the second group taking OXC in add-on with non-enzyme-inducing antiepileptic drugs, and the third group taking OXC in add-on with hepatic-enzyme-inducing antiepileptic drugs or moderate inducers), no significant difference was found between plasma and saliva MHD concentrations in all the above 3 groups. CONCLUSIONS: High correlation between plasma and saliva MHD levels supported the use of saliva as an alternative to plasma for OXC monitoring in children with epilepsy.
Assuntos
Anticonvulsivantes/farmacocinética , Carbamazepina/análogos & derivados , Monitoramento de Medicamentos/métodos , Epilepsia/tratamento farmacológico , Adolescente , Anticonvulsivantes/administração & dosagem , Povo Asiático , Carbamazepina/administração & dosagem , Carbamazepina/farmacocinética , Criança , Pré-Escolar , Cromatografia Líquida de Alta Pressão , Relação Dose-Resposta a Droga , Feminino , Humanos , Lactente , Modelos Lineares , Masculino , Oxcarbazepina , Estudos Prospectivos , Saliva/químicaRESUMO
Hemophilia A is aninherited bleeding disorder, lack of coagulation factor VIII (FVIII), and if combined with intracranial malignant tumor, the operation risk is very high. Department of Pediatric Surgery in Peking University First Hospital used coagulation factor replacement therapy, succeeded in the operation of 2 cases of intracranial malignant tumor with hemophilia A in children, with no abnormal bleeding events. The establishment of the multi subject cooperation group before operation, good preoperative preparation, enough alternative factors, and close postoperative monitoring, are the key to the successful treatment.
Assuntos
Neoplasias Encefálicas/cirurgia , Hemofilia A/complicações , Hemorragia/prevenção & controle , Criança , Humanos , Assistência PerioperatóriaRESUMO
Successful biochemical reactions in organisms necessitate compartmentalization of the requisite components. Glandular trichomes (GTs) act as compartments for the synthesis and storage of specialized compounds. These compounds not only are crucial for the survival of plants under biotic and abiotic stresses but also have medical and commercial value for humans. However, the mechanisms underlying compartmentalization remain unclear. Here we identified a novel structure that is indispensable for the establishment of compartments in cucumber GTs. Silica, a specialized compound, is deposited on the GTs and is visible on the surface of the fruit as a white powder, known as bloom. This deposition provides resistance against pathogens and prevents water loss from the fruits1. Using the cucumber bloomless mutant2, we discovered that a lignin-based cell wall structure in GTs, named 'neck strip', achieves compartmentalization by acting as an extracellular barrier crucial for the silica polymerization. This structure is present in the GTs of diverse plant species. Our findings will enhance the understanding of the biosynthesis of unique compounds in trichomes and provide a basis for improving the production of compounds beneficial to humans.
Assuntos
Cucumis sativus , Lignina , Humanos , Tricomas , Plantas , Dióxido de SilícioRESUMO
Children intestinal inflammatory myofibroblastic tumor (IMT) is rare, and its clinical differential is very difficult to the malignant tumor. Its diagnosis depends on pathology, and operation is the most effective therapy method. We preset here a case of a 5-year-old girl who was admitted to the hospital for intestinal obstruction. A malignant tumor in the intestinal wall showed on the enhanced CT. Exploratory laparotory found the tumor and then it was resected. Postoperative pathology and immunohistochemistry proved that it was an intestinal IMT. Three months' follow-up found no tumor recurrence and metastasis.
Assuntos
Granuloma de Células Plasmáticas/diagnóstico , Intestinos/patologia , Pré-Escolar , Feminino , Humanos , Imuno-HistoquímicaRESUMO
We present an interesting report of a 5-month-old infant with epileptic spasms and developmental delay who presented with non-isolated ventriculomegaly in utero and whose brain magnetic resonance imaging revealed right ventricular choroid plexus papilloma (CPP). The epileptic spasms persisted even with the use of antiepileptic therapies but was apparently cured after the removal of a CPP.
RESUMO
Quartz lamp heaters and hypersonic wind tunnel are currently applied in thermal assessment of heat resistant materials and surface of aircraft. However, it is difficult to achieve precise heat flux distribution by quartz lamp heaters, while enormous energy is required by a large scale hypersonic wind tunnel. Electron beam can be focused into a beam spot of millimeter scale by an electromagnetic lens and electron-magnetically deflected to achieve a rapid scanning over a workpiece. Moreover, it is of high energy utilization efficiency when applying an electron beam to heat a metal workpiece. Therefore, we propose to apply an electron beam with a variable speed to establish a novel method to realize various non-uniform heat flux boundary conditions. Besides, an electron beam thermal assessment equipment is devised. To analyze the feasibility of this method, an approach to calculate the heat flux distribution formed by an electron beam with variable-speed scanning is constructed with beam power, diameter of the beam spot and dwell duration of the electron beam at various locations as the key parameters. To realize a desired non-uniform heat flux distribution of the maximum gradient of 1.1 MW/m3, a variable-speed scanning strategy is constructed on basis of the conservation of energy. Compared with the desired heat flux, the maximum deviation of the scanned heat flux is 4.5% and the deviation in the main thermal assessment area is less than 3%. To verify the method, taking the time-average scanned heat flux as the boundary condition, a heat transfer model is constructed and temperature results are calculated. The experiment of variable-speed scanning of an electron beam according to the scanning strategy has been carried out. The measured temperatures are in good agreement with the predicted results at various locations. Temperature fluctuation during the scanning process is analyzed, and it is found to be proportional to the scanned heat flux divided by volumetric heat capacity, which is applicable for different materials up to 3.35 MW/m2. This study provides a novel and effective method for precise realization of various non-uniform heat flux boundary conditions.
RESUMO
OBJECTIVE: To analyze the cause and treatment of intracranial hypertension after sylvian cystoperitoneal shunting. METHODS: Sixteen cases were retrospectively reviewed. There were 10 males and 6 females. The age range was 2-19 years old (mean: 9.94). All patients had a sylvian cystoperitoneal shunt via a common low-pressure tube. RESULTS: The onset time of intracranial hypertension after cystoperitoneal shunting was 3 months to 7 years (mean: 3.20 yr). Three cases underwent the operation of adjusting intracranial location of shunt tube. The original tube was removed in 12 cases. Among them, 10 cases were operated by lateral ventricle-peritoneal shunt. The other two and two cases with a remaining tube were treated successfully with dehydration drugs. CONCLUSION: The cause of intracranial hypertension is probably due to tube blockage or less draining after the shrinking or disappearance of arachnoid cyst. Adjusting the location of intracranial tube or performing a lateral ventricle-peritoneal shunt has an excellent efficacy if a dehydration therapy is unresponsive or auto-compensation fails.
Assuntos
Derivações do Líquido Cefalorraquidiano/efeitos adversos , Hipertensão Intracraniana/etiologia , Hipertensão Intracraniana/terapia , Adolescente , Cistos Aracnóideos/cirurgia , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Estudos Retrospectivos , Adulto JovemRESUMO
BACKGROUND: Hypothalamic hamartomas (HHs) are rare, and it is even rarer when combined with gray matter heterotopia (GMH) and polymicrogyria (PMG). CASE DESCRIPTION: A 5-year-old boy with HH, GMH, and PMG was retrospectively evaluated. The clinical data, including the symptoms, examinations, diagnosis, and treatment, were collected. The patient had a chief complaint of gelastic seizures and intellectual deficiency. Brain magnetic resonance imaging showed HH, paraventricular nodular heterotopia, and PMG. Video electroencephalographs were normal. The patient underwent resection of the HH via transcallosal transseptal interforniceal approach. Seizures disappeared immediately after complete resection of HH, and the intellectual development improved. CONCLUSIONS: In this extremely rare case, resection of the HH eliminated the symptoms. Nonetheless, we still need to be cautious about the possible epilepsy that may be caused by GMH and PMG.
Assuntos
Substância Cinzenta/patologia , Hamartoma/patologia , Doenças Hipotalâmicas/patologia , Polimicrogiria/patologia , Pré-Escolar , Hamartoma/cirurgia , Humanos , Doenças Hipotalâmicas/cirurgia , Deficiência Intelectual/etiologia , Masculino , Procedimentos Neurocirúrgicos/métodos , Convulsões/etiologiaRESUMO
OBJECTIVE: To analyze the clinical characteristics of patients with hydrocephalus secondary to cobalamin C (cblC) deficiency and to discuss the optimal strategies for assessing and treating such patients by performing clinical and laboratory studies in 70 patients. METHODS: A total of 1,211 patients were clinically diagnosed with methylmalonic acidemia (MMA) from 1998 to 2019. Among them, cblC deficiency was confirmed in 70 patients with hydrocephalus by brain imaging and biochemical and genetic analysis. RESULTS: Of the 70 patients, 67 (95.7%) had early-onset MMA and homocystinuria. The patients typically had high blood propionylcarnitine and total homocysteine, low methionine, and methylmalonic aciduria. Signs of intracranial hypertension were relatively rare. We measured ventricular dilatation early in the disease by cranial ultrasound and MRI and/or CT. Eighteen different MMACHC mutations, including 4 novel mutations (c.427C>T, c.568insT, c.599G>A, and c.615C>A), were identified biallelically in all 70 patients. c.609G>A was the most frequent mutation, followed by c.658_660del, c.217C>T, and c.567dupT. Three cases were diagnosed by postmortem study. Metabolic therapy, including cobalamin injections supplemented with oral l-carnitine and betaine, was administered in the remaining 67 cases. A ventriculoperitoneal shunt was performed in 36 cases. During the follow-up, psychomotor development, nystagmus, impaired vision, and sunset eyes improved gradually. CONCLUSION: Hydrocephalus is a severe condition with several different causes. In this study, ventriculomegaly was found in 70 patients with cblC deficiency. Early diagnosis, etiologic treatment, and prompt surgical intervention are crucial to improve the prognosis of patients.
Assuntos
Erros Inatos do Metabolismo dos Aminoácidos , Hidrocefalia , Derivação Ventriculoperitoneal , Deficiência de Vitamina B 12 , Vitamina B 12/administração & dosagem , Complexo Vitamínico B/administração & dosagem , Erros Inatos do Metabolismo dos Aminoácidos/complicações , Erros Inatos do Metabolismo dos Aminoácidos/tratamento farmacológico , Criança , Pré-Escolar , Feminino , Humanos , Hidrocefalia/diagnóstico por imagem , Hidrocefalia/etiologia , Hidrocefalia/cirurgia , Lactente , Recém-Nascido , Imageamento por Ressonância Magnética , Masculino , Oxirredutases/genética , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Ultrassonografia , Deficiência de Vitamina B 12/complicações , Deficiência de Vitamina B 12/tratamento farmacológico , Deficiência de Vitamina B 12/genéticaRESUMO
BACKGROUND: Cobalamin C deficiency (cblC) caused by the MMACHC mutations is the most common type of the disorders of intracellular cobalamin metabolism. While the c.609G > A mutation is most frequent in Chinese cblC patients, its correlation with phenotype has not been delineated. Here we aim to investigate the factors affecting variable phenotypes and outcomes associated with the MMACHC c.609G > A homologous mutation in 149 Chinese cases to have implications for treatment and prevention. METHODS: We assessed 149 cblC patients caused by MMACHC c.609G > A homozygous mutation. The clinical manifestations, complications, treatment, and outcomes were evaluated; 120 patients were followed-up till December 2019. RESULTS: Two patients (1.3%) were prenatally diagnosed, treated after birth and consequently showed normal development. In 15 patients (10.1%) detected by newborn screening, 10 were treated at the age of 2 weeks and showed normal development, while the other 5 were treated after onset and showed neurologic disorders. All 132 clinically diagnosed patients (88.6%) developed symptoms at age from few minutes after birth to 72 months. Among them, 101 (76.5%) had early-onset (before the age of 12 months) and 31 (23.5%) had late-onset (after the age of 12 months). Totally 5 patients died and 24 were lost to follow-up. Of the 132 clinical diagnosed patients, 92 (69.7%) presented with developmental delay, 65 (49.2%) had seizures, 37 (28.0%) had anemia, 24 (18.2%) had feeding difficulty, 23 (17.4%) had ocular problems, and 22 (16.7%) had hydrocephalus. Compared with the non-developmental delay group, the onset age, the age at treatment initiation and the time from onset to treatment initiation were later in the developmental delay group. Seizure group showed significantly higher urinary methylmalonic acid concentration. During long-term follow-up, plasma total homocysteine (tHcy) levels were significantly higher in patients in the uncontrolled group than those in the seizure-free group. CONCLUSIONS: Most cblC patients caused by MMACHC c.609G > A homozygous mutation showed early-onset. The clinically diagnosed patients usually showed the presence of irreversible brain disorders. Patients treated from the pre-symptomatic stage showed favorable outcomes. Therefore, newborn screening, prenatal diagnosis and early treatment are crucial and the c.609G > A mutant allele should be listed in the pre-pregnancy carrier screening panel in China.
Assuntos
Erros Inatos do Metabolismo dos Aminoácidos , Homocistinúria , Deficiência de Vitamina B 12 , Criança , China , Feminino , Seguimentos , Humanos , Lactente , Recém-Nascido , Mutação/genética , Oxirredutases/genética , Fenótipo , Gravidez , Vitamina B 12RESUMO
OBJECTIVE: To summarize the post-operative complications of resection of hypothalamic hamartoma (HH) through transcallosal transseptal interforniceal approach. METHODS: Thirty-seven HH patients, 26 males and 11 females, aged 8.7 underwent resection of the tumor via the transcallosal transseptal interforniceal approach. The symptoms and blood electrolytes were observed. RESULTS: After operation blood electrolyte test showed that 8 cases were normal, 19 cases showed hyponatremia as prime abnormality, and 10 cases had hypernatremia primarily. Among the 19 cases with hyponatremia transient apathy occurred in 2 cases, general epilepsy occurred in one patient, continuous minor epilepsy occurred in another one, 4 patients suffered minor epilepsy, 25 had fever the temperature of 3 of which were beyond 40 degrees C, and 2 had transient diabetes insipidus and 1 had diabetes. CONCLUSION: Resection of HH through the transcallosal transseptal interforniceal approach achieves significant improvement of gelastic seizures with fewer complications. The most common complication is disturbance of serum natrium, which, however, is mild and well managed.
Assuntos
Hamartoma/cirurgia , Doenças Hipotalâmicas/cirurgia , Procedimentos Neurocirúrgicos/efeitos adversos , Complicações Pós-Operatórias , Adolescente , Adulto , Criança , Pré-Escolar , Corpo Caloso/cirurgia , Feminino , Seguimentos , Humanos , Doenças Hipotalâmicas/patologia , Lactente , Masculino , Procedimentos Neurocirúrgicos/métodos , Septo Pelúcido/cirurgia , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Seizure is the second-most common presentation in patients with arteriovenous malformations (AVMs) and superimposes a significant burden on pediatric patients. Postoperative seizure risk in unruptured AVMs is underreported in the pediatric AVM literature. We aimed to characterize and identify predictive factors for postoperative seizures in this study. METHODS: We performed a retrospective review of all surgically treated pediatric patients with unruptured AVM at our institution from 2001 to 2014. Patients younger than 18 years of age were included. Baseline variables was compared against our outcome of interest, which was defined as patients with or without follow-up seizures. Multivariable Cox regression was performed to identify potential predictive factors. RESULTS: The average age of all patients was 13.1 years, and 68.2% were male. Nine patients were asymptomatic (13.6%), and seizure presentation occurred in 57.6% (n = 38). During an average follow-up of 4.2 years, 12 (18.2%) patients experienced postoperative seizures, with 5 (17.9%) of 28 patients with seizures being de novo. In patients with seizure presentation, 81.6% were completely seizure-free throughout follow-up. In multivariable analysis, larger AVM size (hazard ratio [HR] 1.63, P = 0.023) and temporal location (HR 8.35, P = 0.007) were found to increase the risk of follow-up seizures. On the contrary, seizure presentation (HR 1.91, P = 0.369) and postoperative infection (HR 2.37, P = 0.265) were not associated. CONCLUSIONS: Surgery may eliminate most seizures with low risk of inducing de novo seizures in pediatric patients with unruptured AVM. Predictive factors for postoperative seizures included large AVM size and temporal location. For selected unruptured AVMs with small size and nontemporal location, consideration of surgery as primary treatment for persistent seizures is a reasonable option.
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Malformações Arteriovenosas Intracranianas/cirurgia , Procedimentos Neurocirúrgicos , Complicações Pós-Operatórias , Convulsões/etiologia , Adolescente , Criança , Feminino , Seguimentos , Humanos , Masculino , Procedimentos Neurocirúrgicos/efeitos adversos , Período Pós-Operatório , Radiocirurgia/métodos , Estudos Retrospectivos , Fatores de Risco , Convulsões/diagnóstico , Resultado do Tratamento , Adulto JovemRESUMO
Secreted protein acidic and rich in cysteine (SPARC) gene has been shown to be epigenetically silenced in several cancers. We investigated the loss of expression and promoter methylation of this tumor suppressor gene in gastric cancers and correlated the data with clinicopathological features. We observed the loss of SPARC mRNA and SPARC protein expression in 7 of 10 (70%) gastric cancer cell lines. Upon treatment of expression-negative cell lines with a demethylating agent, expression of mRNA and protein was restored in all cells. Methylation rate of SPARC gene was 80% in ten gastric cancer cell lines and 74% (163 of 220) in primary tumors, while it was 5% in normal gastric mucosa (n = 40). In intestinal gastric cancer, SPARC methylation correlated with a negative prognosis (P < 0.001; relative risk 2.754, 95% confidence interval 1.780-4.261). Immunostaining revealed that SPARC protein was overexpressed in stromal fibroblasts adjacent to neoplastic epithelium but rarely expressed in the primary gastric cancer cells. These results implicate SPARC promoter methylation as an important factor in the tumorigenesis of gastric carcinomas and provide new insights into the potential use of SPARC as a novel biomarker and the potential clinical importance in human gastric cancers.