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1.
Neuroendocrinology ; 2021 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-34763342

RESUMO

BACKGROUND: Hypothalamic injury causes several complicated neuroendocrine-associated disorders, such as water-electrolyte imbalance, obesity, and hypopituitarism. Among these, central diabetes insipidus (CDI), characterized by polyuria, polydipsia, low urine specific gravity, and deficiency of arginine vasopressin contents, is a typical complication after hypothalamic injury. METHODS: CDI was induced by hypothalamic pituitary stalk injury in male animals. Behavioral parameters and blood sample were collected to evaluate the characteristics of body fluid metabolism imbalance. The brains were harvested for high-throughput RNA sequencing and immunostaining to identify pathophysiological changes in corresponding hypothalamic nuclei. RESULTS: Based on transcriptomic analysis, we demonstrated the upregulation of the Atf3/c-Jun axis and identified Lgals3, a microglial activation related gene, as the most significant target gene in response to the body fluid imbalance in CDI. Furthermore, we found that the microglia possessed elevated phagocytic ability, which could promote the elimination of arginine vasopressin neurons after hypothalamic injury. CONCLUSION: Our findings suggested that the Atf3/c-Jun/Lgals3 axis was associated with the microglial activation, and might participate in the loss of functional arginine vasopressin neurons in CDI after hypothalamic injury.

2.
Br J Neurosurg ; : 1-7, 2021 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-34612789

RESUMO

PURPOSE: The occiput-axis crossing translaminar screw (C2LAM) fixation technique can help avoid vertebral injury, while the inclusion of offset connectors can facilitate implantation. This three-dimensional finite element (FE) study compared the stability of C2LAM using offset connectors (C2LAM + OF) with other methods. MATERIALS AND METHODS: Occipital and cervical spine computed tomography images of a healthy 30-year-old man were selected to build the FE model. Four internal fixation instruments including occiput plate-C2 pedicle (C2P) and pars (C2Pars) screws, as well as C2LAM and C2LAM + OF were applied consecutively to the model respectively to establish four new models, which were subjected to all states of motion and physiological loads to simulate normal movement, including the four kinds of basic activities of human such as flexion, extension, lateral bending, and axial rotation. Physiological measures and comparison included the range of motion (ROM) and stress distribution in the model. RESULTS: ROM between the fixation techniques was comparable, and the stability of the C2LAM + OF fixation technique was similar to that of C2P. Screw entry points, offset connectors and rods were the main stress distribution regions in the C2LAM + OF system. The mean von Mises stress of the inner wall was significantly smaller than that of the outer wall in flexion, extension, and rotation (p < 0.05); however, lateral bending was comparable, indicating a relatively small risk of damage to the inner wall. CONCLUSIONS: The results of this study indicate that the C2LAM + OF fusion technique can provide sufficient stability and can be used as an alternative to C2P under special circumstances.

3.
Future Oncol ; 17(33): 4571-4582, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34519220

RESUMO

Aims: To determine how consistently Chinese glioblastoma multiforme (GBM) patients were treated according to the Stupp regimen. Patients and methods: The proportion of treatments conforming to the Stupp regimen and reasons for nonconformity were evaluated in 202 newly diagnosed GBM patients. Results: Only 15.8% of GBM patients received treatments compliant with the Stupp regimen. The main deviations were temozolomide dosages >75 mg/m2 (58/120; 48.3%) and treatment durations <42 days (84/120; 70.0%) in the concomitant phase and temozolomide dosages <150 mg/m2 (89/101; 88.1%) in the maintenance phase. Median overall survival (27.09 vs 18.21 months) and progression-free survival (14.27 vs 12.10 months) were longer in patients who received Stupp regimen-compliant treatments. Conclusion: Increased conformity to the Stupp regimen is needed for GBM patients in China.

4.
Ann Transl Med ; 9(14): 1164, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34430605

RESUMO

Background: An assessment of the clinical impact for craniopharyngiomas (CPs) classification based on origin location has not been reported. The aim of this study was to determine the clinical impact of the site of tumor origin in primary CPs. Methods: Patients from six national institutions who had undergone resection for primary CP were enrolled. Based on the point of origin and surrounding membranous structures, the location of the tumor origin was labelled as Q, S, or T, where Type Q CPs originated below the diaphragmatic area; Type S CPs originated from Rathke's pouch precursor cells; and Type T CPs originated from the Rathke's pouch precursor cells located above the pars tuberalis. Clinical characteristics, surgical approach, and outcome were evaluated according to the location of the tumor origin. Results: Among the 529 patients with primary CP, symptoms, age, histopathology type, tumor size, the incidence of hydrocephalus, survival rates, and recurrence-free survival rates were significantly different among tumors originating in different locations. Patients with type T CPs had higher symptom rates of intracranial hypertension and hypothalamic dysfunction, while those with type Q CPs had higher rates of hormone deficits during pre-and post-operative management. Type S CPs were correlated with better outcomes and lower recurrence rates. The location of origin and primary therapy with survival and recurrence in CP were independent factors for survival and recurrence in multivariate analysis. Conclusions: The identification of the different location of origin of CPs is of great significance in understanding the relationship between tumors and peripheral tissues. The origin of tumors effects the choice of surgical approach and prognosis.

5.
Anticancer Drugs ; 2021 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-34232949

RESUMO

Epithelioid glioblastoma (E-GBM) is a recently described variant of glioblastoma (GBM) which is associated with short survival and now added as a provisional entity to WHO 2016 classification of central nervous system tumors. About half of these tumors show the BRAF mutant. Therefore, this is a target of special interest for this group of patients. Meanwhile, unlike conventional glioblastoma, E-GBM lacks specific prognostic markers. We described a case of a long-term surviving 37-years-old men patient diagnosed with a BRAF V600E and TERT mutated E-GBM with wild-type in the isocitrate dehydrogenase gene (IDH wild-type). The tumor displayed atypical exophytic growth, an obvious proliferation of vascular endothelial cells, especially tumor tissue can be seen under subarachnoid space. Notably, tumor tissue was found under subarachnoid space. After postoperative conventional treatment options were exhausted, vemurafenib treatment was initiated. The patient remained clinically stable, and follow-up magnetic resonance images were consistent with stable disease for the following fifteen months up to now. Whole-exome sequencing analysis and RNA-seq results of formalin-fixed and paraffin-embedded tissue revealed nine mutant genes (AHNAK2, BFSP1, BRAF, CNTNAP3, DNHD1, MTOR, NFATC3, NOM1). For E-GBM patients, the use of BRAF inhibitors combined with inhibitors of these seven genes may be a useful remedial treatment option.

6.
Ann Transl Med ; 9(9): 762, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-34268375

RESUMO

Background: Glioma is the most common and fatal primary cranial tumor. The epidermal growth factor receptor (EGFR) plays an important role in the occurrence and treatment of glioma, which might function through a circular ribonucleic acid (circRNA)-related mechanism. Hsa_circ_0080229 (circ_0080229) has been identified as a circRNA arising from an EGFR gene in gliomas; however, little is known about its molecular mechanism to date. Methods: To address this question, a series of experiments were conducted to confirm the effect of circ_0080229 in gliomas and identify the downstream mechanism. A quantitative real-time polymerase chain reaction (qRT-PCR) analysis and in-situ hybridization/fluorescence in-situ hybridization (ISH/FISH) testing were performed to identify the expression of circ_0080229 in patient samples. Bioinformatic analysis was carried out to explore the possible mechanism. Next, a series of in-vitro functional assays and in-vivo assays with a xenograft subcutaneous glioma model was carried out to confirm the effect of circ_0080229. Finally, qRT-PCR analysis and a Western Blot analysis were performed to verify the related mechanism. Results: The expression of circ_0080229 was upregulated in both glioma tissues and cell lines related to unfavorable clinicopathologic characteristics. The expression of circ_0080229 was found to be inversely correlated with miR-1827, a micro-ribonucleic acid (miRNA) targeting murine double minute-2 (MDM2). The downregulation of circ_0080229 inhibited gliomas in vivo and suppressed U87 and U251 cell lines in vitro, which the transfection of the miR-1827 inhibitor could reverse. Concerning the mechanism, a block of circ_0080229 decreased MDM2 expression, while the inhibition of miR-1827 reversed this effect. Thus, circ_0080229 appears to target the downstream miR-1827/MDM2 signaling pathway. Conclusions: Our results showed that the silencing of circ_0080229 upregulates the expression of miR-1827, which in turn resulted in the suppression of MDM2, and the mediation of the downstream P53 signaling pathway. Circ_0080229 exerted an effect in mediating tumor progression through the MDM2 signaling pathway by sponging miR-1827. Its importance as a potential prognostic biomarker in gliomas has thus been established.

8.
Neuro Oncol ; 23(10): 1693-1708, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34042961

RESUMO

BACKGROUND: The glioblastoma (GBM) mesenchymal (MES) phenotype, induced by NF-κB activation, is characterized by aggressive tumor progression and poor clinical outcomes. Our previous analysis indicated that MES GBM has a unique alternative splicing (AS) pattern; however, the underlying mechanism remains obscure. We aimed to reveal how splicing regulation contributes to MES phenotype promotion in GBM. METHODS: We screened novel candidate splicing factors that participate in NF-κB activation and MES phenotype promotion in GBM. In vitro and in vivo assays were used to explore the function of RSRP1 in MES GBM. RESULTS: Here, we identified that arginine/serine-rich protein 1 (RSRP1) promotes the MES phenotype by facilitating GBM cell invasion and apoptosis resistance. Proteomic, transcriptomic, and functional analyses confirmed that RSRP1 regulates AS in MES GBM through mediating spliceosome assembly. One RSRP1-regulated AS event resulted in skipping PARP6 exon 18 to form truncated, oncogenic PARP6-s. This isoform was unable to effectively suppress NF-κB. Cotreatment of cultured GBM cells and GBM tumor-bearing mice with spliceosome and NF-κB inhibitors exerted a synergistic effect on MES GBM growth. CONCLUSION: We identified a novel mechanism through which RSRP1-dependent splicing promotes the GBM MES phenotype. Targeting AS via RSRP1-related spliceosomal factors might constitute a promising treatment for GBM.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Proteínas de Neoplasias/genética , Animais , Neoplasias Encefálicas/genética , Linhagem Celular Tumoral , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Glioblastoma/genética , Camundongos , NF-kappa B/genética , NF-kappa B/metabolismo , Fenótipo , Proteômica , Spliceossomos/genética , Spliceossomos/metabolismo
9.
CNS Neurosci Ther ; 27(8): 908-918, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33942536

RESUMO

INTRODUCTION AND AIMS: At present, the treatment for moyamoya disease (MMD) primarily consists of combined direct and indirect bypass surgery. Nevertheless, more than half of indirect bypass surgeries fail to develop good collaterals from the dura and temporal muscle. This study aimed to investigate whether microRNAs (miRNAs) in cerebrospinal fluid (CSF) could serve as biomarkers for the prediction of postoperative collateral formation. METHODS: Moyamoya disease patients with indirect bypass surgery were divided into angiogenesis and non-angiogenesis groups, CSF was obtained, and miRNA sequencing was performed using the CSF. Candidate miRNAs were filtered and subsequently verified through qRT-PCR. The diagnostic utility of these differential miRNAs was investigated by using receiver operating characteristic (ROC) curve analysis. Finally, the potential biological processes and signaling pathways associated with candidate miRNAs were analyzed using R software. RESULTS: The expression levels of four miRNAs (miR-92a-3p, miR-486-3p, miR-25-3p, and miR-155-5p) were significantly increased in the angiogenesis group. By combining these four miRNAs (area under the curve [AUC] =0.970), we established an accurate predictive model of collateral circulation after indirect bypass surgery in MMD patients. GO and KEGG analyses demonstrated a high correlation with biological processes and signaling pathways related to angiogenesis. CONCLUSION: The 4-miRNA signature is a good model to predict angiogenesis after indirect bypass surgery and help the surgeon to select a appreciate bypass strategy.

10.
Ann Transl Med ; 9(8): 713, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33987411

RESUMO

Background: Astrocytoma and glioblastoma (GBM) are the two main subtypes of glioma, with the 2016 World Health Organization Classification of Tumors of the Central Nervous System (CNS WHO) classifying them into different grades. GBM is the most malignant among all CNS tumors with a 5-year survival rate of less than 5%. Although the prognosis of patients with astrocytoma is better than that of GBM in general, patients with anaplastic astrocytoma (AA) and isocitrate dehydrogenase (IDH) wild type have a similar prognosis as GBM and entail a high risk of progression. Exploring the molecular driving force behind the malignant phenotype of astrocytoma and GBM will help explain the diversity of glioma and discover new drug targets. Methods: We enrolled 12 patients with astrocytoma and 12 patients with GBM and performed whole-exome sequencing (WES) and RNA sequencing analysis on tumor samples from the patients. Results: We found that the somatic mutation of KRT18, which is associated with cell apoptosis and adhesion by interacting with receptor 1-associated protein (TRADD) and pinin, was significantly enriched in astrocytoma, but rare in GBM. Copy number loss of MTAP, which is closely related to a poor prognosis of glioma, was found to be significantly enriched in GBM. In addition, different somatic copy number alteration (SCNA), gene expression, and immune cell infiltration patterns between astrocytoma and GBM were found. Conclusions: This study revealed the distinct characteristics of astrocytoma and GBM at the DNA and RNA level. Somatic mutation of KRT18 and copy number loss of MTAP, two key genetic alterative genes in astrocytoma and GBM, have the potential to become therapeutic targets in glioma.

11.
World Neurosurg ; 152: e11-e22, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33857671

RESUMO

OBJECTIVE: Serum sodium abnormalities are one of the most common manifestations after radical craniopharyngioma (CP) excision. The aim of this study was to report the incidence and possible predictors of serum sodium disturbance and explore features of sodium destabilization manifestation among QST classification results after CP resection. METHODS: A retrospective analysis was performed of clinical, biochemical, radiologic, and operative data for 134 successive patients who underwent primary CP removal between September 2016 and March 2018. Univariate and multivariate analyses were conducted to determine predictors. RESULTS: Sixty patients (44.8%) experienced hyponatremia and 67 patients (50%) hypernatremia; the median time of onset was 6 days and the first day after surgery, respectively. The incidence, onset, severity, and type of sodium disturbance among different types of CP differed significantly based on statistical tests (P < 0.05). Sodium disturbance was more common and severe in patients with type T tumors (P < 0.05). Age, tumor type, and preoperative diabetes insipidus were independent prognostic factors for obvious disorders of serum sodium. CONCLUSIONS: Hyponatremia/hypernatremia is common after primary CP resection. The site of tumor origin has a direct effect on the growth pattern of CP, which may serve as a useful index for anticipating sodium perturbation after surgery. The level of sodium in children and patients with type T tumors, preoperative diabetes insipidus should be monitored closely throughout hospitalization.


Assuntos
Craniofaringioma/classificação , Craniofaringioma/epidemiologia , Hipernatremia/epidemiologia , Hiponatremia/epidemiologia , Neoplasias Hipofisárias/classificação , Neoplasias Hipofisárias/epidemiologia , Complicações Pós-Operatórias/epidemiologia , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Craniofaringioma/cirurgia , Feminino , Humanos , Hipernatremia/sangue , Hipernatremia/diagnóstico , Hiponatremia/sangue , Hiponatremia/diagnóstico , Incidência , Masculino , Pessoa de Meia-Idade , Neoplasias Hipofisárias/cirurgia , Complicações Pós-Operatórias/sangue , Complicações Pós-Operatórias/diagnóstico , Valor Preditivo dos Testes , Estudos Retrospectivos , Adulto Jovem
12.
Cancer Cell Int ; 21(1): 148, 2021 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-33663520

RESUMO

BACKGROUND: Transmembrane protein with EGF-like and two follistatin-like domains 2 (TMEFF2) is a transmembrane protein in the tomoregulin family. Little research has been performed to determine whether TMEFF2 methylation is a prognostic marker in adult diffuse gliomas. METHODS: In this study, we investigated TMEFF2 expression in surgical glioma tissue samples. In addition, we conducted bisulfite amplicon sequencing (BSAS) and methylation-specific PCR (MSP) to evaluate TMEFF2 methylation in glioblastoma (GBM) cells. Subsequently, we investigated the biological function of TMEFF2 in GBM cells. Moreover, we explored the prognostic significance of TMEFF2 in gliomas by analysing a cohort dataset from TCGA. RESULTS: Immunohistochemistry analysis of 75 paired glioma tumour and peritumoural tissues demonstrated that glioma tumour tissues expressed lower TMEFF2 levels than peritumoural tissues (P < 0.001). TMEFF2 promoter methylation levels were increased in glioblastoma cells compared with SVG p12 cells (P < 0.001). Inhibition of methylation reduced TMEFF2 methylation and increased its expression in LN229 and T98G cells (P < 0.05). Knockdown of TMEFF2 expression significantly promoted the proliferation of U87MG cells and primary GBM cells (P < 0.05). TMEFF2 methylation is negatively associated with IDH1, ATRX and TP53 mutations, and the subtype of glioma harbouring combined IDH1/ATRX/TP53 mutations was associated with low TMEFF2 methylation levels. Survival analysis confirmed that low TMEFF2 methylation levels are associated with good prognosis in glioma patients. CONCLUSIONS: Our results suggest that TMEFF2 DNA methylation might be associated with glioma tumour progression and could serve as a valuable prognostic marker for adult diffuse gliomas.

13.
J Neurosurg ; : 1-12, 2021 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-33668037

RESUMO

OBJECTIVE: An assessment of the transcranial approach (TCA) and the endoscopic endonasal approach (EEA) for craniopharyngiomas (CPs) according to tumor types has not been reported. The aim of this study was to evaluate both surgical approaches for different types of CPs. METHODS: A retrospective review of primary resected CPs was performed. A QST classification system based on tumor origin was used to classify tumors into 3 types as follows: infrasellar/subdiaphragmatic CPs (Q-CPs), subarachnoidal CPs (S-CPs), and pars tuberalis CPs (T-CPs). Within each tumor type, patients were further arranged into two groups: those treated via the TCA and those treated via the EEA. Patient and tumor characteristics, surgical outcomes, and postoperative complications were obtained. All variables were statistically analyzed between surgical groups for each tumor type. RESULTS: A total of 315 patients were included in this series, of whom 87 were identified with Q-CPs (49 treated via TCA and 38 via EEA); 56 with S-CPs (36 treated via TCA and 20 via EEA); and 172 with T-CPs (105 treated via TCA and 67 via EEA). Patient and tumor characteristics were equivalent between both surgical groups in each tumor type. The overall gross-total resection rate (90.5% TCA vs 91.2% EEA, p = 0.85) and recurrence rate (8.9% TCA vs 6.4% EEA, p = 0.35) were similar between surgical groups. The EEA group had a greater chance of visual improvement (61.6% vs 35.8%, p = 0.01) and a decreased risk of visual deterioration (1.6% vs 11.0%, p < 0.001). Of the patients with T-CPs, postoperative hypothalamic status was better in the TCA group than in the EEA group (p = 0.016). Postoperative CSF leaks and nasal complication rates occurred more frequently in the EEA group (12.0% vs 0.5%, and 9.6% vs 0.5%; both p < 0.001). For Q-CPs, EEA was associated with an increased gross-total resection rate (97.4% vs 85.7%, p = 0.017), decreased recurrence rate (2.6% vs 12.2%, p = 0.001), and lower new hypopituitarism rate (28.9% vs 57.1%, p = 0.008). The recurrence-free survival in patients with Q-CPs was also significantly different between surgical groups (log-rank test, p = 0.037). The EEA required longer surgical time for T-CPs (p = 0.01). CONCLUSIONS: CPs could be effectively treated by radical surgery with favorable results. Both TCA and EEA have their advantages and limitations when used to manage different types of tumors. Individualized surgical strategies based on tumor growth patterns are mandatory to achieve optimal outcomes.

14.
Mol Neurobiol ; 58(6): 2780-2791, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33501625

RESUMO

Epilepsy is a common and serious complication of subarachnoid hemorrhage (SAH), giving rise to increased morbidity and mortality. It's difficult to identify patients at high risk of epilepsy and the application of anti-epileptic drugs (AEDs) following SAH is a controversial topic. Therefore, it's pressingly needed to gain a better understanding of the risk factors, underlying mechanisms and the optimization of therapeutic strategies for epilepsy after SAH. Neuroinflammation, characterized by microglial activation and the release of inflammatory cytokines, has drawn growing attention due to its influence on patients with epilepsy after SAH. In this review, we discuss the risk factors for epilepsy after SAH and emphasize the critical role of microglia. Then we discuss how various molecules arising from pathophysiological changes after SAH activate specific receptors such as TLR4, NLRP3, RAGE, P2X7R and initiate the downstream inflammatory pathways. Additionally, we focus on the significant responses implicated in epilepsy including neuronal excitotoxicity, the disruption of blood-brain barrier (BBB) and the change of immune responses. As the application of AEDs for seizure prophylaxis after SAH remains controversial, the regulation of neuroinflammation targeting the key pathological molecules could be a promising therapeutic method. While neuroinflammation appears to contribute to epilepsy after SAH, more comprehensive experiments on their relationships are needed.


Assuntos
Epilepsia/complicações , Inflamação/patologia , Microglia/patologia , Hemorragia Subaracnóidea/complicações , Animais , Barreira Hematoencefálica/patologia , Epilepsia/patologia , Humanos , Fatores de Risco , Hemorragia Subaracnóidea/patologia
15.
Nan Fang Yi Ke Da Xue Xue Bao ; 41(1): 69-74, 2021 Jan 30.
Artigo em Chinês | MEDLINE | ID: mdl-33509755

RESUMO

OBJECTIVE: To establish a mouse model bearing orthotopic temozolomide (TMZ)-resistant glioma that mimics the development of drug resistance in gliomas in vivo. METHODS: Seventy-eight adult C57BL/6 mice were randomly divided into 6 groups (n=13), including 3 TMZ induced groups with low, medium and high doses (5, 25, and 50 mg/kg, respectively) and 3 control groups. In each group, 5 mice were used for evaluating tumor size, 5 for observing survival, and 3 for collecting tumor tissues for primary cell culture. In low-dose TMZ induced group, 3 mice bearing orthotopic murine glioma GL261 cell xenografts received intraperitoneal injections of 5 mg/kg TMZ for 5 days followed by a 10-day washout period before collecting glioma tissues. Tumor cell suspensions were prepared and injected in the mice in the medium-dose group, which were treated with the same protocol but with an increased TMZ dose, and the tumor cells harvested from 3 mice were injected in the high-dose group. The mice bearing GL261 cell xenografts in the 3 control groups received no treatment or were injected with medium- or high-dose TMZ. Cell colony forming assay was used to assess TMZ resistance of each generation of the tumor cells; CCK8 assay was used to determine drug resistance index of the cells. RESULTS: The mouse models bearing TMZresistant glioma was successfully established. The cells from the high-dose induced group showed a significantly higher colony-forming rate than those from the high-dose control group (P < 0.05), and had a drug resistance 4.25 times higher than that of the cells from untreated control group. High-dose TMZ significantly reduced the tumor volume in the control group (P < 0.05) but not in the high-dose induced group (P < 0.01). The survival time of the tumor-bearing mice was significantly shortened in the high-dose induced group (P=0.0018). CONCLUSIONS: Progressive increase of TMZ doses in mice bearing orthotopic gliomas can effectively induce TMZ resistance of the gliomas.


Assuntos
Neoplasias Encefálicas , Glioma , Animais , Antineoplásicos Alquilantes/farmacologia , Neoplasias Encefálicas/tratamento farmacológico , Linhagem Celular Tumoral , Modelos Animais de Doenças , Resistencia a Medicamentos Antineoplásicos , Glioma/tratamento farmacológico , Camundongos , Camundongos Endogâmicos C57BL , Temozolomida/farmacologia , Temozolomida/uso terapêutico
16.
J Neurol Surg A Cent Eur Neurosurg ; 82(2): 112-117, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33157564

RESUMO

BACKGROUND AND STUDY AIMS: The exact reason of long-term survival in glioblastoma (GBM) patients has remained uncertain. Molecular parameters in addition to histology to define malignant gliomas are hoped to facilitate clinical, experimental, and epidemiological studies. MATERIAL AND METHODS: A population of GBM patients with similar clinical characteristics (especially similar resectability) was reviewed to compare the molecular variables between poor (overall survival [OS] < 18 months, control cohort) and long-term survivors (overall survival > 36 months, OS-36 cohort). RESULTS: Long-term GBM survivors were younger. In the OS-36 cohort, the positive rate of isocitrate dehydrogenase (IDH) mutation was very low (7.69%, 3/39) and there was no statistical difference in OS between IDH mutant and wild-type patients. The results of 1p/19q codeletions are similar. Besides, there were no significant difference in MGMT promoter methylation, telomerase reverse transcriptase (TERT) promoter mutation, and TP53 mutations between OS-36 cohort and control cohort. CONCLUSIONS: No distinct markers consistently have been identified in long-term survivors of GBM patients, and great importance should be attached to further understand the biological characteristics of the invasive glioma cells because of the nature of diffuse tumor permeation.


Assuntos
Neoplasias Encefálicas/mortalidade , Glioblastoma/mortalidade , Isocitrato Desidrogenase/genética , Mutação , Telomerase/genética , Adulto , Fatores Etários , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/cirurgia , Estudos de Coortes , Metilação de DNA , Feminino , Glioblastoma/genética , Glioblastoma/patologia , Glioblastoma/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Regiões Promotoras Genéticas , Taxa de Sobrevida
17.
Pediatr Res ; 89(5): 1119-1125, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-32559758

RESUMO

BACKGROUND: The relationship between clinical responses in pediatric infradiaphragmatic craniopharyngioma (Q-CP) and inflammatory response is still unclear. The objective of this study was to investigate the clinical significance of tumor inflammatory response in pediatric Q-CPs. METHODS: The inflammatory response was evaluated by measuring the number of inflammatory cells in the tumor near adenohypophysis junction. The specimens were classified as mild, moderate, or severe based on the number of inflammatory cells. In addition, the levels of pro-inflammatory cytokines and chemokines in the specimens were measured using a cytokine antibody array. Clinical outcomes were analyzed and compared to the markers of inflammatory response. RESULTS: IL-6 and IL-8 were highly expressed in pediatric Q-CPs, and the transcription level of IL-6 was the highest in the severe group. Most patients (87.3%) had hypopituitarism; the severe inflammation group had an increased incidence of hypopituitarism, which correlated with significantly lower probability of recurrence-free survival and worsened functional status. CONCLUSIONS: Inflammatory response is common in craniopharyngiomas and is closely related to their biological behavior and the patients' clinical prognosis. Further studies of the relationship between craniopharyngiomas and the inflammatory response will enable the discovery of potential therapeutic targets, which will reduce morbidity and result in better outcomes for pediatric Q-CP patients. IMPACT: Pediatric infradiaphragmatic craniopharyngiomas are histologically benign brain tumors that often follow an aggressive clinical course. The inflammatory response in craniopharyngioma is common, which is closely related to the biological behavior and clinical prognosis. Several inflammatory and immune markers have been identified in CP; inflammation is an important role in the pathogenesis of hypopituitarism. The aim was to study the relationship between craniopharyngioma and inflammatory response and find potential therapeutic targets can reduce morbidity and result in better outcomes.

18.
Pituitary ; 24(2): 159-169, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33044631

RESUMO

BACKGROUND: Craniopharyngioma represents a troublesome tumor of the intracranial sellar region. There are currently no available well-characterized craniopharyngioma cell lines. This lack of reliable, immortal cell lines is a major reason for the slow progress in fundamental research related to craniopharyngioma. METHODS: We describe the development of an immortal papillary craniopharyngioma (PCP) cell line by transfecting primary PCP cells with the pLenti-simian virus 40 large T antigen(SV40LT). RESULTS: Three clones have been cultured for more than 14 months so far, while non-transfected cells ceased proliferation within three months of isolation. The established immortal PCP cell lines were identified to have BRAFV600E mutations, while no mutations in tumor suppressor genes were found in primary cells or immortal cells. Immortal cells had higher proliferation rates and formed tumors when implanted in the bran of nude mice. BRAF inhibition in immortal PCP cells altered cell morphology, inhibited cell proliferation and promoted apoptosis. CONCLUSION: We successfully developed PCP cell lines by SV40LT-mediated immortalization. These cell lines represent a powerful tool for fundamental and therapeutical studies on craniopharyngioma.

19.
J Clin Neurosci ; 79: 74-79, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33070923

RESUMO

BACKGROUND: Primary central nervous system T-cell lymphoma (PCNSTCL) is a rare neoplasm with few data regarding its common features and survival characteristics. OBJECTIVE: To explore the Surveillance, Epidemiology, and End Results 18 (SEER 18) database to determine the epidemiology of PCNSTCL. METHODS: The SEER 18 registry database was queried to identify patients diagnosed with PCNSTCL from 1973 to 2014 and extract their information. Age-specific rates and Kaplan-Meier overall survival (OS) were calculated. A Cox proportional hazards model was applied to investigate relationships between various demographic/treatment variables and OS. RESULTS: The age-specific incidence rates were higher in the older population (≥60 years). Among 59 PCNSTCL cases from the SEER 18, the mean age at presentation was 55.8 years (SD, ±17.95), with a male predominance (1.36:1.00). The median follow-up was 8 months, and the median OS was 8 months (SE, ±4.162). The 1-, 3-, and 5-year OS was 46.3% [95% CI, 33.4%-59.2%], 32.8% [20.3%-45.3%], and 32.8% [20.3%-45.3%], respectively. Seventeen of the 59 patients survived at last follow-up. Patients < 60 years had a greater 3-year OS compared with patients ≥ 60 years (52.6% [33.6%-71.6%] vs 13.9% [1.4%-26.4%]. Multivariate analysis has demonstrated that only age at diagnosis (≥60/<60 years) exhibited a significant relationship with OS (HR, 3.495 [1.688-7.235];p = 0.001). Sex (female/male) was observed to have a doubted trend towards significance (HR, 0.487 [0.231-1.030]; p = 0.060). CONCLUSIONS: PCNSTCL is generally of poor prognosis but younger age at diagnosis (<60 years) predicts a better prognosis.


Assuntos
Neoplasias do Sistema Nervoso Central/epidemiologia , Linfoma de Células T/epidemiologia , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Programa de SEER
20.
Front Neurosci ; 14: 548278, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33100957

RESUMO

Background: Moyamoya disease (MMD) is an important cause of stroke in children and young adults in Asia. To date, diagnosis remains challenging due to varying clinical manifestations and unknown pathogenesis. The study aims to identify cerebrospinal fluid (CSF) exosomal microRNAs (exomiRs) that can serve as a novel diagnostic biomarker for diagnosis and assess its clinical applications. Methods: CSF samples were taken from 31 MMD patients and 31 healthy controls. Initial screening of miRNA expression was performed on samples pooled from MMD patients and controls using microarray and validated using quantitative reverse transcription polymerase chain reaction (qRT-PCR). The diagnostic accuracy of the potential exosomal miRNAs was evaluated using receiver operating characteristic curve analyses in an independent patient cohort. The potential pathways regulated by the miRNAs was also determined using bioinformatics analysis. Results: The microarray results demonstrated that six exomiRs were dysregulated in the MMD patients compared to the controls. Using qRT-PCR, we validated four of the miRNAs (miR-3679-5p, miR-6165, miR-6760-5p, and miR-574-5p) as a biomarker for MMD diagnosis. The four exomiRs showed enhanced sensitivity (75%) and specificity (93.75%) in terms of differentiating MMD patients from healthy subjects [area under the curve (AUC) = 0.9453]. Pathway enrichment analysis for potential targets of six exomiRs identified proteins involved in cell adhesion and junction formation in the brain. Conclusions: We identified a novel and highly sensitive exomiRs signature for MMD detection and explored its potential targets using bioinformatics analysis.

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