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Background: Gliomas constitute a category of malignant tumors originating from brain tissue, representing the majority of intracranial malignancies. Previous research has demonstrated the pivotal role of CLEC7A in the progression of various cancers, yet its specific implications within gliomas remain elusive. The primary objective of this study was to investigate the prognostic significance and immune therapeutic potential of CLEC7A in gliomas through the integration of bioinformatics and clinical pathological analyses. Methods: This investigation involved examining and validating the relationship between CLEC7A and glioma using samples from Hospital, along with data from TCGA, GEO, GTEx, and CGGA datasets. Subsequently, we explored its prognostic value, biological functions, expression location, and impact on immune cells within gliomas. Finally, we investigated its potential impact on the chemotaxis and polarization of macrophages. Results: The expression of CLEC7A is upregulated in gliomas, and its levels escalate with the malignancy of tumors, establishing it as an independent prognostic factor. Functional enrichment analysis revealed a significant correlation between CLEC7A and immune function. Subsequent examination of immune cell differential expression demonstrated a robust association between CLEC7A and M2 macrophages. This conclusion was further substantiated through single-cell analysis, immunofluorescence, and correlation studies. Finally, the knockout of CLEC7A in M2 macrophages resulted in a noteworthy reduction in macrophage chemotaxis and polarization factors. Conclusion: CLEC7A expression is intricately linked to the pathology and molecular characteristics of gliomas, establishing its role as an independent prognostic factor for gliomas and influencing macrophage function. It could be a promising target for immunotherapy in gliomas.
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Neoplasias Encefálicas , Glioma , Lectinas Tipo C , Macrófagos , Microambiente Tumoral , Humanos , Glioma/inmunología , Glioma/genética , Glioma/patología , Microambiente Tumoral/inmunología , Microambiente Tumoral/genética , Lectinas Tipo C/genética , Lectinas Tipo C/metabolismo , Pronóstico , Neoplasias Encefálicas/inmunología , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patología , Macrófagos/inmunología , Macrófagos/metabolismo , Biomarcadores de Tumor/genética , Regulación Neoplásica de la Expresión Génica , Macrófagos Asociados a Tumores/inmunología , Macrófagos Asociados a Tumores/metabolismoRESUMEN
Objective:To explore the methods of resection, dura and skull base repair and reconstruction of cranionasal communication tumor. Methods:Data of 31 patients with cranionasal communication tumor who underwent dura and skull base reconstruction after tumor resection from 2018 to 2022 were collected. Follow-up lasted for 3 to 41 months. Results:A total of 31 patients were enrolled, including 20 males and 11 females. The ages ranged from 19 to 74 years, with a median age of 57 years old. There were 17 benign lesionsï¼one case of hemangioma, one case of Rathke cyst, one case of squamous papilloma, one case of craniopharyngioma, two cases of meningocele, two cases of varus papilloma, two cases of meningioma of grade â , three cases of schwannoma, four cases of pituitary tumorï¼ and 14 malignant lesionsï¼one case of osteosarcoma, one case of poorly differentiated carcinoma, two cases of varus papilloma malignancy, two cases of olfactory neuroblastoma, two cases of adenocarcinoma, two cases of adenoid cystic carcinoma, four cases of squamous cell carcinomaï¼ . Sixteen cases underwent nasal endoscopy combined with craniofacial incision and 15 cases underwent nasal endoscopy surgery alone. Complete resection of the mass and dura and skull base reconstruction were performed in all 31 patients, and free graft repair was performed in 8 casesï¼fascia lata in 5 cases and nasal mucosa in 3 casesï¼. Twenty-three cases were repaired with pedicled flapsï¼septal mucosal flap alone in 11 cases, septal mucosal flap combined with free graft in 6 cases, and cap aponeurosis combined with free graft in 6 casesï¼. Eight out of 31 patients underwent skull base bone repair. Postoperative cerebral hemorrhage occurred in 1 case, cerebrospinal fluid leakage in 1 case, intracranial infection in 2 cases. All patients were successfully treated without severe sequelae. Cerebrospinal fluid leakage and intracranial infection occurred in one patient after radiotherapy, who recovered after conservative treatment. All 17 patients with benign lesions survived. Thirteen out of 14 patients with malignant lesions received radiotherapy after surgery, nine survived without recurrence, five cases recurred, of which 2 survived with tumor, one underwent reoperation and 2 died. Conclusion:Cranionasal communication tumors are high-risk diseases of anterior and middle skull base, and various surgical repair methods could be selected after complete resection of the tumor. Successful reconstruction and multidisciplinary cooperation are crucial for treatment outcome.
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Procedimientos de Cirugía Plástica , Base del Cráneo , Humanos , Masculino , Persona de Mediana Edad , Femenino , Adulto , Procedimientos de Cirugía Plástica/métodos , Anciano , Base del Cráneo/cirugía , Adulto Joven , Duramadre/cirugía , Neoplasias de la Base del Cráneo/cirugíaRESUMEN
Background Cerebral blood volume (CBV) maps derived from dynamic susceptibility contrast-enhanced (DSC) MRI are useful but not commonly available in clinical scenarios. Purpose To test image-to-image translation techniques for generating CBV maps from standard MRI sequences of brain tumors using the bookend technique DSC MRI as ground-truth references. Materials and Methods A total of 756 MRI examinations, including quantitative CBV maps produced from bookend DSC MRI, were included in this retrospective study. Two algorithms, the feature-consistency generative adversarial network (GAN) and three-dimensional encoder-decoder network with only mean absolute error loss, were trained to synthesize CBV maps. The performance of the two algorithms was evaluated quantitatively using the structural similarity index (SSIM) and qualitatively by two neuroradiologists using a four-point Likert scale. The clinical value of combining synthetic CBV maps and standard MRI scans of brain tumors was assessed in several clinical scenarios (tumor grading, prognosis prediction, differential diagnosis) using multicenter data sets (four external and one internal). Differences in diagnostic and predictive accuracy were tested using the z test. Results The three-dimensional encoder-decoder network with T1-weighted images, contrast-enhanced T1-weighted images, and apparent diffusion coefficient maps as the input achieved the highest synthetic performance (SSIM, 86.29% ± 4.30). The mean qualitative score of the synthesized CBV maps by neuroradiologists was 2.63. Combining synthetic CBV with standard MRI improved the accuracy of grading gliomas (standard MRI scans area under the receiver operating characteristic curve [AUC], 0.707; standard MRI scans with CBV maps AUC, 0.857; z = 15.17; P < .001), prediction of prognosis in gliomas (standard MRI scans AUC, 0.654; standard MRI scans with CBV maps AUC, 0.793; z = 9.62; P < .001), and differential diagnosis between tumor recurrence and treatment response in gliomas (standard MRI scans AUC, 0.778; standard MRI scans with CBV maps AUC, 0.853; z = 4.86; P < .001) and brain metastases (standard MRI scans AUC, 0.749; standard MRI scans with CBV maps AUC, 0.857; z = 6.13; P < .001). Conclusion GAN image-to-image translation techniques produced accurate synthetic CBV maps from standard MRI scans, which could be used for improving the clinical evaluation of brain tumors. Published under a CC BY 4.0 license. Supplemental material is available for this article. See also the editorial by Branstetter in this issue.
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Neoplasias Encefálicas , Glioma , Humanos , Volumen Sanguíneo Cerebral , Estudios Retrospectivos , Recurrencia Local de Neoplasia , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/patología , Imagen por Resonancia Magnética/métodos , Glioma/diagnóstico por imagen , Glioma/patologíaRESUMEN
Background: Siglec15 is rising as a promising immunotherapeutic target in bladder, breast, gastric, and pancreatic cancers. The aim of the present study is to explore the prognostic value and immunotherapeutic possibilities of Siglec15 in gliomas using bioinformatics and clinicopathological methods. Methods: The bioinformatics approach was used to examine Siglec15 mRNA expression in gliomas based on TCGA, CGGA, and GEO datasets. Then, the predictive value of Siglec15 expression on progression-free survival time (PFST) and overall survival time (OST) in glioma patients was comprehensively described.The TCGA database was screened for differentially expressed genes (DEGs) between the high and low Siglec15 expression groups, and enrichment analysis of the DEGs was performed. The Siglec15 protein expression and its prognostic impact in 92 glioma samples were explored using immunohistochemistry Next, the relationships between Siglec15 expression and infiltrating immune cells, immune regulators and multiple immune checkpoints were analysed. Results: Bioinformatics analyses showed that high Siglec15 levels predicted poor clinical prognosis and adverse recurrence time in glioma patients. In the immunohistochemical study serving as a validation set, Siglec15 protein overexpression was found in 33.3% (10/30) of WHO grade II, 56% (14/25) of WHO grade III, and 70.3% (26/37) of WHO grade IV gliomas respectively. Siglec15 protein overexpression was also found to be an independent prognostic indicator detrimental to the PFST and OST of glioma patients. Enrichment analysis showed that the DEGs were mainly involved in pathways associated with immune function, including leukocyte transendothelial migration, focal adhesion, ECM receptor interaction, and T-cell receptor signaling pathways. In addition, high Siglec15 expression was related to M2 tumor-associated macrophages (TAMs), N2 tumor-infiltrating neutrophils, suppressive tumor immune microenvironment, and multiple immune checkpoint molecules. Immunofluorescence analysis confirmed the colocalization of Siglec15 and CD163 on TAMs. Conclusion: Siglec15 overexpression is common in gliomas and predicts an adverse recurrence time and overall survival time. Siglec15 is a potential target for immunotherapy and a potential TAMs regulator that is involved in the suppressed immunomicroenvironment in gliomas.
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Glioma , Neoplasias Pancreáticas , Humanos , Glioma/genética , Macrófagos , Pronóstico , Microambiente Tumoral/genética , Macrófagos Asociados a TumoresRESUMEN
Ventriculoperitoneal shunt (VPS) placement is the standard procedure in the management of hydrocephalus. The introduction of laparoscopy allows better visualization during the operation and a more reliable placement of the peritoneal terminal of the catheter, which significantly decreases postoperative obstruction and malposition rates. However, the fixation methods of the peritoneal terminal of the catheter have not been previously discussed. The indications, techniques, and complications were compared between conventional VPS and laparoscopy-guided VPS. Furthermore, same analyses were performed within the laparoscopy-guided VPS group subdivided by three different techniques of the fixation of the peritoneal terminal of catheter, including suture and ligature, titanium clip fixation, and subcutaneous fixation. A total of 137 patients with hydrocephalus who received VPS treatment was retrospectively studied, 85 of which were laparoscopy-guided, and 52 were not. The distal ends of the catheters were all placed in the suprahepatic space. At least one year (mean 28.6 months) follow-up was given postoperatively. The average duration of the whole operation was 45 min for suture and ligature, 40 min for titanium clip fixation, and 30 min for the subcutaneous fixation, respectively. Six patients (4.4%) had obstructive of the ventricular catheter in total. The success rates for the laparoscopy-assisted VPS procedure and the conventional VPS procedure were 87.1% (74/85) and 80.8% (42/52), respectively. Within subgroups of the laparoscopy-assisted VPS divided by fixation methods, the procedures were successful in 85.2% (23/27) of suture and ligation, 82.1% (23/28) of titanium clip fixation, and 93.3% (28/30) of subcutaneous fixation, respectively. Two patients had dislocated shunt tube in peritoneal end in laparoscopy group, all in the titanium clip fixation subgroups. The laparoscopy-assisted VPS insertion is an ideal shunt method for its effectiveness and lesser complication rate after operation. The subcutaneous fixation method of the peritoneal terminal of catheter might be the optimal fixation technique.
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Hidrocefalia , Laparoscopía , Humanos , Derivación Ventriculoperitoneal , Estudios Retrospectivos , Titanio , Laparoscopía/métodos , Hidrocefalia/cirugíaRESUMEN
The water-selective channel protein aquaporin-4 (AQP4) contributes to the migration and proliferation of gliomas, and to their resistance to therapy. Here we show, in glioma cell cultures, in subcutaneous and orthotopic gliomas in rats, and in glioma tumours in patients, that transmembrane water-efflux rate is a sensitive biomarker of AQP4 expression and can be measured via conventional dynamic-contrast-enhanced magnetic resonance imaging. Water-efflux rates correlated with stages of glioma proliferation as well as with changes in the heterogeneity of intra-tumoural and inter-tumoural AQP4 in rodent and human gliomas following treatment with temozolomide and with the AQP4 inhibitor TGN020. Regions with low water-efflux rates contained higher fractions of stem-like slow-cycling cells and therapy-resistant cells, suggesting that maps of water-efflux rates could be used to identify gliomas that are resistant to therapies.
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Glioma , Agua , Humanos , Ratas , Animales , Agua/metabolismo , Glioma/diagnóstico por imagen , Glioma/metabolismo , Acuaporina 4/metabolismo , Biomarcadores , Imagen por Resonancia MagnéticaRESUMEN
Sepsis-associated encephalopathy (SAE) is a life-threatening deterioration of mental status in relation to long-term and disabling cognitive dysfunction that is common in intensive care units worldwide. Cortistatin-14 is a neuropeptide structurally resembling somastostatin, which has been proven to play a crucial role in sepsis. The present study aimed to explore the neuroprotective role of cortistatin-14 in sepsis-associated encephalopathy and its underlying mechanisms in a mouse model. A septic mice model was established using the cecal ligation and puncture (CLP) method. The novel object recognition test (NORT), open field test (OFT), elevated plus maze test (EPMT), and tail suspension test (TST) were used to explore the behavioral performance of the mice. Transmission electron microscopy was used to observe the microstructure of the blood-brain barrier (BBB). Evans Blue staining was used to examine the integrity of the BBB. Immunofluorescence was used to examine the morphology and infiltration of microglia. A multiplex cytokine bead array assay was used to determine cytokine and chemokine levels in mouse serum and brain tissues. NORT revealed that cortistatin treatment improved cognitive impairment in septic mice. OFT, EPMT, and TST indicated that cortistatin-14 relieved the anxiety-related behaviors of CLP mice. In addition, cortistatin-14 treatment decreased the levels of various inflammatory cytokines, including interleukin-1ß, interleukin-6, interferon-γ, and tumor necrosis factor-α in both the serum and brain of septic mice. Cortistatin reduced sepsis-induced blood-brain barrier disruption and inhibited microglial activation after the onset of sepsis. Cortistatin exerts neuroprotective effects against SAE and cognitive dysfunction in a CLP-induced mouse model of sepsis.
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Disfunción Cognitiva , Neuropéptidos , Fármacos Neuroprotectores , Encefalopatía Asociada a la Sepsis , Sepsis , Animales , Barrera Hematoencefálica , Disfunción Cognitiva/tratamiento farmacológico , Disfunción Cognitiva/etiología , Citocinas/metabolismo , Modelos Animales de Enfermedad , Azul de Evans , Interferón gamma , Interleucina-1beta , Interleucina-6 , Ratones , Microglía/metabolismo , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/uso terapéutico , Péptidos Cíclicos , Sepsis/complicaciones , Sepsis/tratamiento farmacológico , Sepsis/patología , Encefalopatía Asociada a la Sepsis/tratamiento farmacológico , Factor de Necrosis Tumoral alfaRESUMEN
Malignant triton tumor (MTT) is a rare kind of malignant peripheral nerve sheath tumors, histologically characterized by rhabdomyoblastic differentiation. There are limited reports of MTT occurring in the intracranial area. The treatment modality consisting of total surgical resection plus post-operative radiotherapy is generally accepted. However, even with optimal treatment, most patients will die within a few months. We report a 71-year-old man with a history of pituitary adenoma, who underwent surgical treatment and postoperative gamma knife therapy. Magnetic resonance imaging (MRI) of the brain revealed a mass with two distinctive components in the sellar area. Postoperative pathology found that the lesion consisted of a MTT and a relapsed pituitary adenoma. The present case is the first report of MTT that occurred in the sellar area. It is also the first case of intracranial MTT with other concurrent tumors (relapsed pituitary tumors). Meanwhile, this case has a clear history of radiation therapy, suggesting that the occurrence of MTT may be related to radiation.
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Context: Ganoderic acid A (GAA) is usually used to prevent cancers or other diseases, which make it likely to be used with other drugs metabolized by cytochromes P450.Objective: This study investigates the effect of GAA on eight major cytochrome P450 isoforms in human liver microsomes.Material and method: The effects of GAA (100 µM) on eight human liver CYP isoforms (i.e., 1A2, 3A4, 2A6, 2E1, 2D6, 2C9, 2C19, and 2C8) were investigated in vitro using human liver microsomes (HLMs) with specific substrates for the CYPs, and the enzyme kinetic parameters were calculated.Results: The results showed that GAA inhibited the activity of CYP3A4, 2D6, and 2E1, but did not affect other isoforms. The inhibition of CYP3A4, 2D6, and 2E1 was concentration-dependent with IC50 values of 15.05, 21.83, and 28.35 µM, respectively. Additionally, GAA was not only a non-competitive inhibitor of CYP3A4, but also a competitive inhibitor of CYP2D6 and 2E1, with Ki values of 7.16, 10.07, and 13.45 µM. Meanwhile, the inhibition of CYP3A4 was time-dependent, with the KI/Kinact value of 7.91/0.048 µM/min.Discussion and conclusion: The in vitro study indicated that GAA has the potential to result in drug-drug interactions with other drugs metabolized by CYP3A4, 2D6, and 2E1. Further clinical studies are needed for the identification of this interaction.
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Inhibidores Enzimáticos del Citocromo P-450/farmacología , Sistema Enzimático del Citocromo P-450/metabolismo , Ácidos Heptanoicos/farmacología , Lanosterol/análogos & derivados , Hígado/efectos de los fármacos , Microsomas Hepáticos/efectos de los fármacos , Interacciones Farmacológicas , Humanos , Cinética , Lanosterol/farmacología , Microsomas Hepáticos/enzimologíaRESUMEN
OBJECTIVES: This study aimed to investigate the feasibility of segmentation-independent volume rendering (SI-VR) in visualising the root entry zone (REZ), and to explore the influence on the management of vascular compression syndromes (VCSs). METHODS: Two hundred and twenty patients with VCSs were recruited in this prospective study from July 2015 to May 2019. SI-VR was reconstructed based on inverted 3D fast spin echo T2WI. They were assigned to the experimental group and control group randomly. Patients in the experimental group would accept extra evaluation based on SI-VR before microvascular decompression. Image quality and diagnostic accuracy between SI-VR and 3D fast spin echo T2WI in the experimental group were compared by Mann-Whitney U test and chi-square test, separately. Interobserver agreement was performed with intraclass correlation coefficient. Postsurgical outcomes and complications between two groups were compared by chi-square test. RESULTS: SI-VR had a better interobserver agreement (0.82 vs 0.68) and diagnostic accuracy (95.5% vs 83.6%, p = 0.004) than that of 3D fast spin echo T2WI. Especially, significantly improved diagnostic accuracy was reached in detecting the multi-vascular branches compression (100% vs 15.4%, p < 0.001). There were fewer complications (7.1% vs 26.8%, p = 0.004) and less operation time (20.7 min vs 14.5 min, p = 0.007) but no significant difference of pain relief (p = 0.19) in the experimental group than in the control group. CONCLUSIONS: The SI-VR method is feasible for the precise demonstration of the anatomy structure along the REZ, with high reliability and reproducibility. Unbiased pre-surgical visualisation could reduce redundant explorations and post-surgical complications in patients who undergo microvascular decompression. KEY POINTS: ⢠Visualisation of the root entry zone by the segmentation-independent volume rendering is in accordance with the landscape by the neuro-endoscopy. ⢠Segmentation-independent volume rendering has an advantage over 3D fast spin echo T2WI in the visualisation of multi-vascular branches compression. ⢠Presurgical 3D visualisation of the neurovascular compression at the root entry zone leads to less postsurgical complications from the decrease of redundant exploration.
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Interpretación de Imagen Asistida por Computador/métodos , Imagenología Tridimensional/métodos , Imagen por Resonancia Magnética/métodos , Cirugía para Descompresión Microvascular/métodos , Complicaciones Posoperatorias/prevención & control , Estudios de Factibilidad , Femenino , Humanos , Masculino , Cirugía para Descompresión Microvascular/efectos adversos , Microvasos/diagnóstico por imagen , Microvasos/cirugía , Persona de Mediana Edad , Estudios Prospectivos , Reproducibilidad de los ResultadosRESUMEN
BACKGROUND: Three-dimensional T1 magnetization prepared rapid acquisition gradient echo (3D-T1-MPRAGE) is preferred in detecting brain metastases (BM) among MRI. We developed an automatic deep learning-based detection and segmentation method for BM (named BMDS net) on 3D-T1-MPRAGE images and evaluated its performance. METHODS: The BMDS net is a cascaded 3D fully convolution network (FCN) to automatically detect and segment BM. In total, 1652 patients with 3D-T1-MPRAGE images from 3 hospitals (n = 1201, 231, and 220, respectively) were retrospectively included. Manual segmentations were obtained by a neuroradiologist and a radiation oncologist in a consensus reading in 3D-T1-MPRAGE images. Sensitivity, specificity, and dice ratio of the segmentation were evaluated. Specificity and sensitivity measure the fractions of relevant segmented voxels. Dice ratio was used to quantitatively measure the overlap between automatic and manual segmentation results. Paired samples t-tests and analysis of variance were employed for statistical analysis. RESULTS: The BMDS net can detect all BM, providing a detection result with an accuracy of 100%. Automatic segmentations correlated strongly with manual segmentations through 4-fold cross-validation of the dataset with 1201 patients: the sensitivity was 0.96â ±â 0.03 (range, 0.84-0.99), the specificity was 0.99â ±â 0.0002 (range, 0.99-1.00), and the dice ratio was 0.85â ±â 0.08 (range, 0.62-0.95) for total tumor volume. Similar performances on the other 2 datasets also demonstrate the robustness of BMDS net in correctly detecting and segmenting BM in various settings. CONCLUSIONS: The BMDS net yields accurate detection and segmentation of BM automatically and could assist stereotactic radiotherapy management for diagnosis, therapy planning, and follow-up.
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Neoplasias Encefálicas , Aprendizaje Profundo , Neoplasias Encefálicas/diagnóstico por imagen , Humanos , Imagenología Tridimensional , Imagen por Resonancia Magnética , Estudios RetrospectivosRESUMEN
Accurate pathological diagnosis of gliomas recurrence is crucial for the optimal management and prognosis prediction. The study here unravels that our newly developed γ-glutamyltranspeptidase (GGT) fluorescence probe (Figure 1A) imaging in twenty recurrent glioma tissues selectively recognizes the most malignant portion from treatment responsive tissues induced by radio/chemo-therapy (Figure 1B). The overexpression of GGT in recurrent gliomas and low level in radiation necrosis were validated by western blot analysis and immunohistochemistry. Furthermore, the ki-67 index evaluation demonstrated the significant increase of malignancy, aided by the GGT-responsive fluorescent probe to screen out the right specimen through fast enhanced imaging of enzyme activity. Importantly, our GGT-targeting probe can be used for accurate determination of pathologic evaluation of tumor malignancy, and eventually for guiding the following management in patients with recurrent gliomas.
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Hemorragias Intracraneales/diagnóstico , Hemorragias Intracraneales/etiología , Vasculitis del Sistema Nervioso Central/complicaciones , Vasculitis del Sistema Nervioso Central/diagnóstico , Adulto , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Colágeno Tipo IV/genética , Diagnóstico Diferencial , Humanos , Hemorragias Intracraneales/tratamiento farmacológico , Hemorragias Intracraneales/patología , Masculino , Recurrencia , Vasculitis del Sistema Nervioso Central/tratamiento farmacológico , Vasculitis del Sistema Nervioso Central/patologíaRESUMEN
PURPOSE: SIL1 is a ubiquitous protein localized to the endoplasmic reticulum and functions as a cochaperone of BiP. Previous studies have shown that function loss of SIL1 is often associated with neurological diseases, such as Marinesco-Sjögren Syndrome. However, no studies have investigated the function of SIL1 in tumors. In this study we aim to reveal functions of SIL1 and the underlying mechanisms in glioma. MATERIALS AND METHODS: First, by searching on Gene Expression Profiling Interactive Analysis, we examined SIL1 expression and prognostic value in glioblastoma multiforme (GBM) and brain lower grade glioma (LGG). Immunohistochemical analysis (IHC) was also performed to determine the endogenic SIL1 level. Cell counting kit-8 (CCK8) and clone formation assays were used to detect cell proliferation of U251 cells. Cell migration was detected by transwell assay and cell cycle and apoptosis were detected by flow cytometry. Western blot was performed to determine protein expression. RESULTS: We found that the expression of SIL1 was increased by approximately 1.5-fold in GBM and 1.3-fold in LGG compared with normal controls (P<0.05) and negatively correlated with patients' survival. IHC revealed that SIL1 expression was significantly higher in glioma tissues than that in paracancerous tissues (P<0.05). Glioma patients with high SIL1 expression accounted for 65.79% (25/38) of total samples and SIL1 expression significantly increased in grade IV glioma compared to grades I-III (P=0.026). Suppression of SIL1 expression led to significant inhibition of U251 cell proliferation. Transwell assay showed that cell migration of U251 was significantly inhibited by siSIL transfection, with an inhibitory rate reaching 69%. Flow cytometry detection showed that siSIL1 could induce apoptosis of U251 cells and upregulated the expression of the pro-apoptotic protein Bax and Caspase3-P17. However, siSIL1 transfection had no effect on the cell cycle. Mechanism studies demonstrated that siSIL1 transfection led to inactivation of AKT/mTOR signaling pathway, including decreased phosphorylation of AKT and mTOR without affecting protein expression, as well as decreased expression of the downstream effector p70S6K. CONCLUSION: Downregulation of SIL1 inhibited the progression of glioma by suppressing the AKT/mTOR signaling pathway.
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BACKGROUND: Intracranial primary collision tumors of different histologic types are rare, and their occurrence is still unclear. CASE DESCRIPTION: We describe a 66-year-old female who presented with headache, nausea, and vomiting. Magnetic resonance imaging scan showed that there were 2 primary intracranial tumors occurring simultaneously at adjacent sites of the right cerebral hemisphere. Tumor pathology showed 2 distinct tumors: meningioma (World Health Organization I) and glioblastoma. This is a rare case in which 2 different intracranial primary tumors occurred at adjacent sites, but the patient had no history of head trauma, neurologic surgery, or radiation therapy. CONCLUSIONS: According to previous and present reports, the most common type of intracranial primary collision tumor is composed of a benign meningioma and a glioblastoma. During the occurrence of collision tumors, 1 tumor can play a role in the formation and growth of the other.
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Neoplasias Encefálicas , Glioblastoma , Neoplasias Meníngeas , Meningioma , Neoplasias Primarias Múltiples , Anciano , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/patología , Neoplasias Encefálicas/cirugía , Femenino , Glioblastoma/diagnóstico por imagen , Glioblastoma/patología , Glioblastoma/cirugía , Humanos , Neoplasias Meníngeas/diagnóstico por imagen , Neoplasias Meníngeas/patología , Neoplasias Meníngeas/cirugía , Meningioma/diagnóstico por imagen , Meningioma/patología , Meningioma/cirugía , Neoplasias Primarias Múltiples/diagnóstico por imagen , Neoplasias Primarias Múltiples/patología , Neoplasias Primarias Múltiples/cirugíaRESUMEN
Distinguishing tumor from adjacent non-cancerous tissue can be problematic during surgical treatment of malignant glioma. Consequently, a novel approach to selective discrimination is required. The goal of this study was to determine whether a fluorescent probe activated by γ-Glutamyltranspeptidase (GGT), an enzyme that is overexpressed on glioma cell membranes but only minimally expressed in normal brain tissue, could be used to visualize glioma margins. Here, we showed that the GGT-activatable fluorescent probe (NC-B-Cys-γ-Glu) provided real-time in situ tracking of enzyme activity that accurately distinguished glioma from healthy brain tissue. NC-B-Cys-γ-Glu, which featured distinct ratiometric fluorescence responsiveness after interaction with GGT, enabled monitoring of GGT activity in living cells and differentiation between glioma and normal cells. Topical spraying of NC-B-Cys-γ-Glu facilitated real-time in vivo identification of orthotopic glioblastomas in a mouse model. Importantly, the tumor, infiltrating area and surrounding normal tissue were distinguished in clinical glioma samples by real-time tracking of GGT activity. When coupled with auto fluorescence bronchoscopy, NC-B-Cys-γ-Glu offered diagnostic value for cancers overexpressing GGT. Therefore, NC-B-Cys-γ-Glu might offer a promising tool to guide maximal yet precise tumor resection while sparing non-cancerous tissue.
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Neoplasias Encefálicas/diagnóstico por imagen , Glioma/diagnóstico por imagen , gamma-Glutamiltransferasa/metabolismo , Adulto , Anciano , Animales , Neoplasias Encefálicas/enzimología , Neoplasias Encefálicas/patología , Línea Celular Tumoral , Supervivencia Celular , Dipéptidos/química , Femenino , Colorantes Fluorescentes/química , Glioma/enzimología , Glioma/patología , Humanos , Masculino , Ratones Desnudos , Persona de Mediana Edad , Imagen ÓpticaRESUMEN
INTRODUCTION: Treatment of recurrent high-grade gliomas (rHGG) has always been challenging. This study aimed to explore the treatment effect of quantitative dynamic susceptibility contrast perfusion-weighted imaging (DSC-PWI)-guided gamma knife radiosurgery (GKRS) on rHGG. METHODS: Between April 2014 and July 2016, 26 consecutive patients were treated by quantitative DSC-PWI-guided GKRS as salvage treatment for rHGG. The gross tumor volume (GTV) was defined as the high perfusion area on absolute cerebral blood volume maps, with a cutoff value of 22 ml/100 g. The clinical target volume (CTV) encompassed the GTV by 3 mm. Overall survival (OS) and progression-free survival (PFS) were calculated by the Kaplan-Meier method. Prognostic factors were tested by the log-rank (Mantel-Cox) test. RESULTS: With a median follow-up of 32 months, the median PFS after GKRS was 8 months (95% CI [6, 12]); the 1- and 2-year survival rates were 30.8 and 11.5%, respectively. The median OS was 25.5 months (95% CI [18, 40]); the 1- and 2-year survival rates were 96.2 and 57.7%, respectively. Pathology grade and CTV were identified as prognostic factors for PFS. However, none of the parameters tested were independent prognostic factors for OS among these selected patients. No severe radiotoxicity was observed among all patients. CONCLUSIONS: Quantitative DSC-PWI-guided GKRS is feasible for the treatment of rHGG and that these outcomes remain to be validated. Despite this, we think that carefully selected patients can benefit from this treatment method.
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Neoplasias Encefálicas/radioterapia , Glioma/radioterapia , Imagen por Resonancia Magnética , Radiocirugia , Radioterapia Guiada por Imagen , Reirradiación , Adolescente , Adulto , Anciano , Antineoplásicos Alquilantes/uso terapéutico , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/mortalidad , Neoplasias Encefálicas/patología , Niño , Medios de Contraste , Femenino , Estudios de Seguimiento , Glioma/diagnóstico por imagen , Glioma/mortalidad , Glioma/patología , Humanos , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Pronóstico , Radiocirugia/métodos , Radioterapia Guiada por Imagen/métodos , Reirradiación/métodos , Temozolomida/uso terapéutico , Carga Tumoral , Adulto JovenRESUMEN
Gliomas are the most common primary malignant brain tumors in adults. Accurate grading is crucial as therapeutic strategies are often disparate for different grades and may influence patient prognosis. This study aims to provide an automated glioma grading platform on the basis of machine learning models. In this paper, we investigate contributions of multi-parameters from multimodal data including imaging parameters or features from the Whole Slide images (WSI) and the proliferation marker Ki-67 for automated brain tumor grading. For each WSI, we extract both visual parameters such as morphology parameters and sub-visual parameters including first-order and second-order features. On the basis of machine learning models, our platform classifies gliomas into grades II, III, and IV. Furthermore, we quantitatively interpret and reveal the important parameters contributing to grading with the Local Interpretable Model-Agnostic Explanations (LIME) algorithm. The quantitative analysis and explanation may assist clinicians to better understand the disease and accordingly to choose optimal treatments for improving clinical outcomes. The performance of our grading model was evaluated with cross-validation, which randomly divided the patients into non-overlapping training and testing sets and repeatedly validated the model on the different testing sets. The primary results indicated that this modular platform approach achieved the highest grading accuracy of 0.90 ± 0.04 with support vector machine (SVM) algorithm, with grading accuracies of 0.91 ± 0.08, 0.90 ± 0.08, and 0.90 ± 0.07 for grade II, III, and IV gliomas, respectively.
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OBJECTIVE: To investigate the association between polymorphisms in the gene encoding activin receptorlike kinase 1 (ACVRL1) with brain arteriovenous malformations (BAVMs) using a case-control study in a Chinese Han population, followed by a meta-analysis of the published literature. METHODS: This study focused on the genotypic analysis of 4 single nucleotide polymorphisms (SNPs; rs2071219, rs706819, rs2293094, and rs11169953) in 50 patients with BAVM and 120 healthy volunteers attending Provincial Hospital in China. A meta-analysis was subsequently conducted involving an extensive literature search for relevant studies. RESULTS: Our cohort study showed a significant association between ACVRL1 rs706819 and increased risk for BAVM. Reduced BAVM risk was correlated with the G allele of rs2293094 and the C allele of rs11169953. However, neither the genotype nor allele frequencies of rs2071219 were found to be significantly different between the BAVM and control groups. Meta-analysis further confirmed that no significant evidence of association was found between rs2071219 and BAVM risk. Haplotype analysis of rs706819, rs2293094, and rs11169953 showed that the GGT haplotype could reduce the risk of BAVM, whereas the GAC haplotype may increase the risk of BAVM. CONCLUSIONS: The present study indicates an association between 3 susceptibility SNPs, rs706819, rs2293094, and rs11169953, in the ACVRL1 gene and BAVM. Follow-up functional studies on the ACVRL1 gene are required to better understand its roles in BAVM development.
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Receptores de Activinas Tipo II/genética , Predisposición Genética a la Enfermedad , Malformaciones Arteriovenosas Intracraneales/genética , Polimorfismo de Nucleótido Simple , Adulto , Pueblo Asiatico/genética , Estudios de Casos y Controles , China , Estudios de Cohortes , Femenino , Frecuencia de los Genes , Estudios de Asociación Genética , Haplotipos , Humanos , Masculino , Modelos GenéticosRESUMEN
Eleated expression of NIMA-related kinase 2 (NEK2) was frequently observed in a variety of malignant cancers, and it appears to be involved in the initiation, maintenance, progression, metastasis of cancer and is positively associated with poor prognosis. We sought to investigate NEK2 expression and its predictive roles in malignant gliomas, and study the correlation of NEK2 protein expression with proliferation, clinical parameters, overall survival and some other parameters. We investigate NEK2 protein expression in 99 samples of malignant gliomas, including 35 WHO grade II, 22 grade III, and 42 grade IV gliomas, by immunohistochemistry and western blot (n = 50). We then made correlative analysis of protein overexpression using the Kaplan-Meier method, Log rank test, and Cox proportional-hazards model analysis. NEK2 protein was overexpressed in malignant gliomas, but not in normal brain tissues. Overexpression of NEK2 correlated with malignancy, proliferation and adverse overall survival in gliomas. Moreover, chemotherapy, resection extent and WHO grade also correlate with overall survival in gliomas. However, within WHO grade II glioma subgroup, NEK2 overexpression showed no impact on overall survival. The present study firstly reveals that NEK2 protein is widely overexpressed in gliomas. NEK2 overexpression correlates significantly with malignancy (WHO grades), proliferation (Ki-67) and prognosis in malignant gliomas. NEK2 is a potential gene therapy target and prognostic indicator.