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1.
Arch. argent. pediatr ; 119(2): e171-e175, abril 2021. ilus
Artigo em Espanhol | LILACS, BINACIS | ID: biblio-1152122

RESUMO

Los tumores del sistema nervioso central representan la segunda enfermedad oncológica más habitual en niños y adolescentes. Entre los tumores intracraneales, los de células germinales son infrecuentes. Los síntomas que desencadenan son cefalea, náuseas, vómitos, déficits hormonales, alteraciones visuales, pérdida de peso, pobre crecimiento y pubertad precoz. Menos frecuentemente, producen trastornos del movimiento o psiquiátricos. Algunos de estos tumores pueden ser asintomáticos un largo período, lo que desencadena un diagnóstico tardío.Se presenta a una paciente femenina de 14 años con pérdida de peso y falla del crecimiento, con diagnóstico erróneo de trastorno de la conducta alimentaria. Tras estudios pertinentes, se arribó al diagnóstico de germinoma del sistema nervioso central. Al ser esta patología infrecuente y de presentación variable, requiere alto sentido de alerta por parte de la familia involucrada y del equipo de salud para evitar retrasos en el diagnóstico y el tratamiento


Central nervous system tumors are the second most frequent oncological disease among children and teenagers. Among the intracranial tumors, the germ cells ones are infrequent. The symptoms they cause are headaches, nausea and vomiting, hormonal deficits, visual disturbances, weight loss, poor growth and early puberty. Less frequently, they produce movement or psychiatric disorders. Some of these tumors can be asymptomatic for a long period leading to a late diagnosis.The case of a 14-year-old female patient is presented. She showed weight loss and growth failure, with wrong diagnosis of eating disorder. After proper study methods, we arrived to central nervous system germinoma diagnosis. Because this pathology is rare and has a variable form of presentation, it requires that the family involved and the health team to be alert, to avoid delays in diagnosis and treatment.


Assuntos
Humanos , Feminino , Adolescente , Germinoma/diagnóstico por imagem , Neoplasias Encefálicas , Perda de Peso , Germinoma/terapia , Insuficiência de Crescimento , Hipopituitarismo
2.
Adv Exp Med Biol ; 1280: 261-276, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33791988

RESUMO

Metabolic reprogramming is an important characteristics of glioma, the most common form of malignant brain tumor. In this chapter, we aim to discuss some of the recently discovered metabolic alterations in glioma, including the dysregulated TCA cycle, amino acid, nucleotide, and lipid metabolism. We have also detailed some of the metabolomic applications in gliomas, particularly the analyses of body fluids and tissues of glioma patients. With new improvement of the technology, metabolomics will become a powerful tool to discover truly meaningful biomarkers for clinical applications in gliomas. Metabolomic studies of gliomas will also facilitate a better understanding of the molecular targets/pathways and the development of new therapeutic treatments for this devastating disease.


Assuntos
Neoplasias Encefálicas , Glioma , Biomarcadores Tumorais/genética , Neoplasias Encefálicas/genética , Ciclo do Ácido Cítrico , Glioma/diagnóstico , Glioma/genética , Humanos , Isocitrato Desidrogenase/genética , Metabolismo dos Lipídeos , Metabolômica , Mutação
3.
Int J Mol Sci ; 22(5)2021 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-33807899

RESUMO

We aimed to evaluate the angiogenic capacity of CXCL2 and IL8 affecting human endothelial cells to clarify their potential role in glioblastoma (GBM) angiogenesis. Human GBM samples and controls were stained for proangiogenic factors. Survival curves and molecule correlations were obtained from the TCGA (The Cancer Genome Atlas) database. Moreover, proliferative, migratory and angiogenic activity of peripheral (HUVEC) and brain specific (HBMEC) primary human endothelial cells were investigated including blockage of CXCR2 signaling with SB225502. Gene expression analyses of angiogenic molecules from endothelial cells were performed. Overexpression of VEGF and CXCL2 was observed in GBM patients and associated with a survival disadvantage. Molecules of the VEGF pathway correlated but no relation for CXCR1/2 and CXCL2/IL8 was found. Interestingly, receptors of endothelial cells were not induced by addition of proangiogenic factors in vitro. Proliferation and migration of HUVEC were increased by VEGF, CXCL2 as well as IL8. Their sprouting was enhanced through VEGF and CXCL2, while IL8 showed no effect. In contrast, brain endothelial cells reacted to all proangiogenic molecules. Additionally, treatment with a CXCR2 antagonist led to reduced chemokinesis and sprouting of endothelial cells. We demonstrate the impact of CXCR2 signaling on endothelial cells supporting an impact of this pathway in angiogenesis of glioblastoma.


Assuntos
Neoplasias Encefálicas , Quimiocina CXCL2/metabolismo , Glioblastoma , Células Endoteliais da Veia Umbilical Humana/metabolismo , Interleucina-8/metabolismo , Proteínas de Neoplasias/metabolismo , Receptores de Interleucina-8B/metabolismo , Transdução de Sinais , Neoplasias Encefálicas/irrigação sanguínea , Neoplasias Encefálicas/patologia , Glioblastoma/irrigação sanguínea , Glioblastoma/metabolismo , Glioblastoma/patologia , Células Endoteliais da Veia Umbilical Humana/patologia , Humanos , Fator A de Crescimento do Endotélio Vascular/metabolismo
4.
Zhonghua Yi Xue Za Zhi ; 101(14): 1031-1035, 2021 Apr 13.
Artigo em Chinês | MEDLINE | ID: mdl-33845543

RESUMO

Objective: To analyze the expression of CXC chemokine ligand 10 (CXCL10) in glioma and its clinical significance through bioinformatics. Methods: The expression level of CXCL10 in glioma, and its prognostic significance, gene ontology (GO) function annotation, Kyoto Encyclopedia of Genes and Genome (KEGG) pathway enrichment and the correlation of tumor cell purity were analyzed in TCGA, CGGA, MetaScape, TIMER databases. In addition, 34 clinical glioma tissues were collected for Western Blot and immunohistochemistry to further verify the correlation between CXCL10 and glioma. Results: CGGA and TCGA database analysis showed that with the increase of WHO grade, the expression of CXCL10 in gliomas increased (P<0.01). The overall survival rate of patients with high CXCL10 expression was significantly lower than that of patients with low expression (χ2 =148.1,P<0.05). Among patients with grade Ⅳ glioblastoma who received radiotherapy or chemotherapy, the patients with low CXCL10 expression were associated with good survival (χ2 =6.714,P<0.05;χ2 =5.618,P<0.05). Moreover, GO and KEGG analysis showed that genes co-expressed with CXCL10 were mainly enriched in the biological processes such as cytokine-mediated signaling pathways, regulating adaptive immune responses and inflammatory responses. Furthermore, TIMER database analysis showed that CXCL10 was negatively correlated with the purity of glioma cells (LGG: r=-0.129;GBM: r=-0.165;P<0.05). Similarly, clinical sample analysis also showed that the expression level of CXCL10 increased in glioma, and it increased with the grade of glioma (all P<0.05). Conclusion: The expression of CXCL10 is up-regulated in glioma as well as it increased with the malignant degree of glioma. At the same time, the high expression of CXCL10 in glioma is closely related to the poor prognosis of patients.


Assuntos
Neoplasias Encefálicas , Quimiocina CXCL10/genética , Glioblastoma , Glioma , Quimiocinas CXC , Humanos , Ligantes
5.
BMC Genomics ; 22(1): 275, 2021 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-33863291

RESUMO

BACKGROUND: Sepsis is the major cause of death in Intensive Care Unit (ICU) globally. Molecular detection enables rapid diagnosis that allows early intervention to minimize the death rate. Recent studies showed that long non-coding RNAs (lncRNAs) regulate proinflammatory genes and are related to the dysfunction of organs in sepsis. Identifying lncRNA signature with absolute abundance is challenging because of the technical variation and the systematic experimental bias. RESULTS: Cohorts (n = 768) containing whole blood lncRNA profiling of sepsis patients in the Gene Expression Omnibus (GEO) database were included. We proposed a novel diagnostic strategy that made use of the relative expressions of lncRNA pairs, which are reversed between sepsis patients and normal controls (eg. lncRNAi > lncRNAj in sepsis patients and lncRNAi < lncRNAj in normal controls), to identify 14 lncRNA pairs as a sepsis diagnostic signature. The signature was then applied to independent cohorts (n = 644) to evaluate its predictive performance across different ages and normalization methods. Comparing to common machine learning models and existing signatures, SepSigLnc consistently attains better performance on the validation cohorts from the same age group (AUC = 0.990 & 0.995 in two cohorts) and across different groups (AUC = 0.878 on average), as well as cohorts processed by an alternative normalization method (AUC = 0.953 on average). Functional analysis demonstrates that the lncRNA pairs in SepsigLnc are functionally similar and tend to implicate in the same biological processes including cell fate commitment and cellular response to steroid hormone stimulus. CONCLUSION: Our study identified 14 lncRNA pairs as signature that can facilitate the diagnosis of septic patients at an intervenable point when clinical manifestations are not dramatic. Also, the computational procedure can be generalized to a standard procedure for discovering diagnostic molecule signatures.


Assuntos
Neoplasias Encefálicas/mortalidade , RNA Longo não Codificante/genética , Sepse/diagnóstico , Estudos de Coortes , Humanos , Sepse/genética
6.
Artigo em Russo | MEDLINE | ID: mdl-33864664

RESUMO

Central neurocytoma is a rare benign brain tumor. These tumors may be giant and accompanied by compression of ventricular system and surrounding structures. Modern treatment of brain neurocytoma includes extended resection and restoration of normal CSF circulation. Surgical treatment does not often lead to total resection of these tumors. Redo resection was preferred in patients with tumor progression for a long time. In the last decade, various authors report stereotactic irradiation for continued tumor growth to ensure local growth control. This study was aimed at evaluation of postoperative outcomes in patients with brain neurocytomas, as well as treatment of tumor progression in long-term period. OBJECTIVE: To analyze recurrence-free survival in patients with brain neurocytomas, risk factors of recurrence-free survival, effectiveness of various treatments for tumor progression and delayed complications. MATERIAL AND METHODS: Long-term postoperative follow-up data of patients with brain neurocytomas are reported in the manuscript. We analyzed recurrence-free survival and risk factors of recurrence-free survival, treatment outcomes in patients with progression of brain neurocytomas, long-term complications and their prevention. RESULTS: Follow-up included 84 out of 115 patients with brain neurocytoma after surgical treatment in 2008-2017. Follow-up period ranged from 2 to 10 years (mean 6 years) after resection. Most patients had regression of neurological symptoms after surgery. Continued tumor growth within 12-96 months after surgery occurred in 26 (30.19%) out of 84 patients (19 cases after partial resection and 7 cases after total resection according to MRI data). Two-year recurrence-free survival was 94%, 5-year survival - 83%. Risk factors of continued tumor growth were resection quality and Ki-67 index. Redo resection was performed in 7 cases. Eleven patients underwent stereotactic irradiation for tumor progression. Indications for stereotactic irradiation of central neurocytoma are MR data on continued growth of lateral ventricle tumor without signs of ICH and CSF flow impairment. There were no cases of hemorrhage inside the residual tumor and CSF flow impairment in early postoperative period after redo resection. In all cases (n=11), stereotactic irradiation (mean follow-up 2.5 years) ensured satisfactory control of tumor growth with reduction of the neoplasm in 4 cases and no tumor growth in 7 cases. CONCLUSION: Resection of central neurocytoma ensures long-term recurrence-free period. The main causes of tumor recurrence are partial resection and high proliferative activity (Ki-67 index over 5%). Redo resection is advisable for tumor progression followed by CSF flow impairment. In case of continued growth of neurocytoma without signs of intracranial hypertension, stereotactic irradiation with various fractionation modes ensures effective and safe control of tumor growth.


Assuntos
Neoplasias Encefálicas , Neurocitoma , Radiocirurgia , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/cirurgia , Seguimentos , Humanos , Recidiva Local de Neoplasia/cirurgia , Neurocitoma/diagnóstico por imagem , Neurocitoma/cirurgia , Resultado do Tratamento
7.
Artigo em Russo | MEDLINE | ID: mdl-33864667

RESUMO

Complex management of patients with intracranial pilocytic astrocytoma (PA) consists of surgical treatment, drug therapy (mainly in young children) and radiotherapy. For many years, radiotherapy (RT) has been a standard for residual tumors, recurrence or continued growth of PA. Currently, stereotactic radiosurgery and radiotherapy are preferred for PA, because these procedures are characterized by high conformity and selectivity, precise irradiation of tumor with minimal damage to surrounding intact tissues. Stereotaxic approach is very important since PAs are localized near functionally significant and radiosensitive brain structures in most cases. There is significant experience of single-center studies devoted to radiotherapy of patients with PA at the Department of Neuroradiosurgery of the Burdenko Neurosurgery Center. In this research, the authors analyzed the results of stereotactic irradiation of 430 patients with PA for the period from 2005 to 2018.


Assuntos
Astrocitoma , Neoplasias Encefálicas , Radiocirurgia , Astrocitoma/diagnóstico por imagem , Astrocitoma/cirurgia , Encéfalo , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/cirurgia , Criança , Pré-Escolar , Humanos
8.
Artigo em Russo | MEDLINE | ID: mdl-33864672

RESUMO

Multiple gliomas are determined by synchronous two or more tumors located in different brain regions. It is important to distinguish multiple primary tumors and metastatic brain lesion. In the first case, tumor spread can`t be explained by dissemination along the cerebrospinal fluid pathways, commissural fibers or local metastases. Multiple primary tumors with different histological structures are called bidermal neoplasms. Surgery is preferred in these patients with severe symptoms. The purpose of surgery is maximum resection of tumor. Follow-up may be advisable for small tumors without clinical manifestations. Treatment of multiple gliomas includes surgery, radiotherapy and chemotherapy. Multiple tumor process in children is much more severe compared to a single neoplasia that requires neurological and neuroimaging control and determines treatment strategy. The authors report 3 children with multicentric gliomas, discuss the various aspects of diagnosis and treatment of multiple gliomas and formulate the recommendations for the treatment based on own clinical experience and literature data.


Assuntos
Neoplasias Encefálicas , Glioma , Neurocirurgia , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/cirurgia , Criança , Glioma/diagnóstico por imagem , Glioma/cirurgia , Humanos , Imagem por Ressonância Magnética , Procedimentos Neurocirúrgicos
9.
Mymensingh Med J ; 30(2): 315-322, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33830108

RESUMO

Astrocytoma is the commonest primary brain tumor. These are feared due to their invasiveness in brain parenchyma so are less amenable to surgical removal and current chemotherapy regimens with a high mortality rate. Cell adhesion molecule (CAM) E-cadherin (CDH1) downregulation has been associated with tumors of different system and organs featuring invasion and metastasis. Therefore, the aim of the study was to find out the level of E-cadherin gene expression in low grade astrocytoma. In this cross-sectional study, 22 formalin fixed paraffin embedded tissue were taken as cases. Three non tumorous brain tissue and 1fresh post-mortem brain tissue were taken as control. Histological features were studied under light microscope with Haematoxylin and Eosin (H&E stain). Expression of CDH1 gene was analyzed by real time - polymerase chain reaction (RT-PCR) by comparative cyclic threshold (Ct) value method. The change in E-cadherin expression was measured by fold change in comparison with the control brain tissue. The data was tabulated and statistical analysis was performed. Among the 22 study cases 8(36.36%) were World Health Organization (WHO) Grade I and 14(63.63%) were WHO Grade II. All tumors showed downregulation of CDH1 gene in comparison with non-tumorous control tissue. The result is statistically significant (p=0.019). So, the study data revealed that downregulation of E-cadherin gene occurs in low grade astrocytoma and tumors of WHO Grade II showed more downregulation than Grade I tumors.


Assuntos
Astrocitoma , Neoplasias Encefálicas , Antígenos CD/genética , Astrocitoma/genética , Neoplasias Encefálicas/genética , Caderinas/genética , Estudos Transversais , Humanos , Reação em Cadeia da Polimerase em Tempo Real
10.
Mymensingh Med J ; 30(2): 420-425, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33830123

RESUMO

Different types of solitary brain lesions and also tumefactive demyelinating lesions exhibit many features on CT and MRI that are characteristics of malignancy and surgical biopsy is often performed in suspected tumour. Proton MR Spectroscopy has been used to differentiate different type of these solitary brain lesions. Our purpose is to determine whether MR spectroscopy is able to improve preoperative diagnostic accuracy in case of intracranial solitary tumors. This cross sectional study was carried out among 44 patients who were referred to Radiology and Imaging Department by Neurosurgery and Neuro-medicine department of BSMMU, Dhaka, Bangladesh as MRI suspected glioma for MRS scan during the period of 24 months. MRS was performed in 44 patients with suspected glioma. Metabolic ratio of choline: Cr, NAA: Cr, Lactate: Cr was calculated in short and intermediated echo times (TES). Tumors were subdivided into neoplasm and inflammatory mass. Neoplasm was again subdivided into glioblastoma multiforme and solitary metastasis. The patients were followed up and surgical resection biopsy reports were collected. MRS findings and histopathological findings were then correlated. In this study 68.18% of patients were diagnosed as Glioblastoma multiform by MRS and also in histopathology 18.18%. Patient was diagnosed as solitary metastasis in MRS and 20.45%. Patient was diagnosed as solitary metastasis by histopathology and 13.64%. Patient was diagnosed as abscess in MRS while in histopathology 11.37% patients were diagnosed as abscess.


Assuntos
Neoplasias Encefálicas , Glioma , Bangladesh , Encéfalo , Neoplasias Encefálicas/diagnóstico por imagem , Estudos Transversais , Humanos , Espectroscopia de Ressonância Magnética
12.
Int J Mol Sci ; 22(7)2021 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-33804873

RESUMO

Different functional states determine glioblastoma (GBM) heterogeneity. Brain cancer cells coexist with the glial cells in a functional syncytium based on a continuous metabolic rewiring. However, standard glioma therapies do not account for the effects of the glial cells within the tumor microenvironment. This may be a possible reason for the lack of improvements in patients with high-grade gliomas therapies. Cell metabolism and bioenergetic fitness depend on the availability of nutrients and interactions in the microenvironment. It is strictly related to the cell location in the tumor mass, proximity to blood vessels, biochemical gradients, and tumor evolution, underlying the influence of the context and the timeline in anti-tumor therapeutic approaches. Besides the cancer metabolic strategies, here we review the modifications found in the GBM-associated glia, focusing on morphological, molecular, and metabolic features. We propose to analyze the GBM metabolic rewiring processes from a systems biology perspective. We aim at defining the crosstalk between GBM and the glial cells as modules. The complex networking may be expressed by metabolic modules corresponding to the GBM growth and spreading phases. Variation in the oxidative phosphorylation (OXPHOS) rate and regulation appears to be the most important part of the metabolic and functional heterogeneity, correlating with glycolysis and response to hypoxia. Integrated metabolic modules along with molecular and morphological features could allow the identification of key factors for controlling the GBM-stroma metabolism in multi-targeted, time-dependent therapies.


Assuntos
Neoplasias Encefálicas/metabolismo , Glioblastoma/metabolismo , Microambiente Tumoral , Animais , Neoplasias Encefálicas/patologia , Glioblastoma/patologia , Humanos , Hipóxia Tumoral
13.
Anticancer Res ; 41(4): 1811-1819, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33813386

RESUMO

BACKGROUND/AIM: Glioblastoma is the most common cancer among primary brain tumors, however, its prognosis and treatment advances are very poor. Here, we investigated whether c-Met, FOLR1, and AXL proteins are promising targets for chimeric antigen receptor (CAR) T-cell therapy, for they are known to be over-expressed in a variety of solid tumors. MATERIALS AND METHODS: CAR constructs were prepared and CAR KHYG-1 cells targeting c-Met, FOLR1, or AXL were made by lentiviral transduction. The activity of CAR KHYG-1 cells against cancer cells was measured by cytokine secretion and cell lysis assays. RESULTS: c-Met and AXL were over-expressed in most glioblastoma cell lines (11/13), but not in neuroblastoma cell lines (0/8). FOLR1 was over-expressed only in one among 16 glioblastoma cell lines. Our antigen-specific CAR KHYG-1 cells eradicated target positive glioblastoma cells selectively. CONCLUSION: Anti-c-Met and anti-AXL CAR NK or T cells could be effective in glioblastoma cells.


Assuntos
Neoplasias Encefálicas/terapia , Glioblastoma/terapia , Imunoterapia Adotiva , Células Matadoras Naturais/imunologia , Proteínas Proto-Oncogênicas c-met/imunologia , Proteínas Proto-Oncogênicas/imunologia , Receptores Proteína Tirosina Quinases/imunologia , Receptores de Antígenos Quiméricos/imunologia , Linfócitos T/imunologia , Neoplasias Encefálicas/imunologia , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Técnicas de Cocultura , Citocinas/metabolismo , Citotoxicidade Imunológica , Receptor 1 de Folato/imunologia , Receptor 1 de Folato/metabolismo , Glioblastoma/imunologia , Glioblastoma/metabolismo , Glioblastoma/patologia , Humanos , Células Jurkat , Células Matadoras Naturais/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Proteínas Proto-Oncogênicas c-met/metabolismo , Receptores Proteína Tirosina Quinases/metabolismo , Receptores de Antígenos Quiméricos/genética , Receptores de Antígenos Quiméricos/metabolismo , Linfócitos T/metabolismo
14.
Anticancer Res ; 41(4): 1859-1870, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33813391

RESUMO

BACKGROUND/AIM: Demethoxycurcumin (DMC), one of the derivatives of curcumin, has been shown to induce apoptotic cell death in many human cancer cell lines. However, there is no available information on whether DMC inhibits metastatic activity in human glioblastoma cancer cells in vitro. MATERIALS AND METHODS: DMC at 1.0-3.0 µM significantly decreased the proliferation of GBM 8401 cells; thus, we used 2.0 µM for further investigation regarding anti-metastatic activity in human glioblastoma GBM 8401 cells. RESULTS: The internalized amount of DMC has reached the highest level in GBM 8401 cells after 3 h treatment. Wound healing assay was used to determine cell mobility and results indicated that DMC suppressed cell movement of GBM 8401 cells. The transwell chamber assays were used for measuring cell migration and invasion and results indicated that DMC suppressed cell migration and invasion in GBM 8401 cells. Gelatin zymography assay was used to examine gelatinolytic activity (MMP-2) in conditioned media of GBM 8401 cells treated by DMC and results demonstrated that DMC significantly reduced MMP-2 activity. Western blotting showed that DMC reduced the levels of p-EGFR(Tyr1068), GRB2, Sos1, p-Raf, MEK, p-ERK1/2, PI3K, p-Akt/PKBα(Thr308), p-PDK1, NF-κB, TIMP-1, MMP-9, MMP-2, GSK3α/ß, ß-catenin, N-cadherin, and vimentin, but it elevated Ras and E-cadherin at 24 h treatment. CONCLUSION: DMC inhibited cancer cell migration and invasion through inhibition of PI3K/Akt and NF-κB signaling pathways in GBM 8401 cells. We suggest that DMC may be used as a novel anti-metastasis agent for the treatment of human glioblastoma cancer in the future.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Neoplasias Encefálicas/tratamento farmacológico , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Diarileptanoides/farmacologia , Glioblastoma/tratamento farmacológico , Fosfatidilinositol 3-Quinase/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Neoplasias Encefálicas/enzimologia , Neoplasias Encefálicas/patologia , Linhagem Celular Tumoral , Glioblastoma/enzimologia , Glioblastoma/patologia , Humanos , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , NF-kappa B/metabolismo , Invasividade Neoplásica , Transdução de Sinais , beta Catenina/metabolismo
15.
Medicine (Baltimore) ; 100(15): e25586, 2021 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-33847690

RESUMO

RATIONALE: Although renal cell carcinoma (RCC) is one of the common origins of brain metastasis, few cases of extremely delayed brain metastasis from RCC, more than 10 years after nephrectomy, have been reported. We present a rare case of extremely delayed brain metastasis from RCC, also performed a literature review to increase knowledge of the characteristics for extremely delayed brain metastasis from RCC. PATIENT CONCERNS: A 72-year-old man presented with right-sided hemiplegia and dysarthria. The patient had a history of radical nephrectomy for RCC with stage T1N0M0 15 years earlier. DIAGNOSIS: Magnetic resonance imaging with contrast revealed a 2-cm sized non-homogenous enhanced mass in the left frontal lobe with peritumoral edema. The pathological examination after surgery reported metastatic clear cell RCC. INTERVENTIONS: A craniotomy for removal of the mass was performed at the time of diagnosis. Stereotactic radiosurgery was performed for the tumor bed 3 weeks after craniotomy, and then, chemotherapy was started 2 months after the SRS. OUTCOMES: Metastasis progressed to multiple organs 6 months after the craniotomy. The patient chose a hospice and no longer visited the hospital. LESSONS: In cases with a history of nephrectomy for RCC, long period follow-up is necessary for monitoring RCC brain metastasis and pathologic diagnosis should be confirmed.


Assuntos
Neoplasias Encefálicas/secundário , Carcinoma de Células Renais/secundário , Neoplasias Renais/patologia , Nefrectomia/métodos , Idoso , Neoplasias Encefálicas/cirurgia , Carcinoma de Células Renais/cirurgia , Craniotomia , Evolução Fatal , Humanos , Neoplasias Renais/cirurgia , Masculino , Período Pós-Operatório , Radiocirurgia , Fatores de Tempo
16.
Sensors (Basel) ; 21(6)2021 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-33810176

RESUMO

Brain tumor classification plays an important role in clinical diagnosis and effective treatment. In this work, we propose a method for brain tumor classification using an ensemble of deep features and machine learning classifiers. In our proposed framework, we adopt the concept of transfer learning and uses several pre-trained deep convolutional neural networks to extract deep features from brain magnetic resonance (MR) images. The extracted deep features are then evaluated by several machine learning classifiers. The top three deep features which perform well on several machine learning classifiers are selected and concatenated as an ensemble of deep features which is then fed into several machine learning classifiers to predict the final output. To evaluate the different kinds of pre-trained models as a deep feature extractor, machine learning classifiers, and the effectiveness of an ensemble of deep feature for brain tumor classification, we use three different brain magnetic resonance imaging (MRI) datasets that are openly accessible from the web. Experimental results demonstrate that an ensemble of deep features can help improving performance significantly, and in most cases, support vector machine (SVM) with radial basis function (RBF) kernel outperforms other machine learning classifiers, especially for large datasets.


Assuntos
Neoplasias Encefálicas , Aprendizado de Máquina , Neoplasias Encefálicas/diagnóstico por imagem , Humanos , Imagem por Ressonância Magnética , Redes Neurais de Computação , Máquina de Vetores de Suporte
17.
Nat Commun ; 12(1): 2184, 2021 04 12.
Artigo em Inglês | MEDLINE | ID: mdl-33846316

RESUMO

Glioblastomas are hierarchically organised tumours driven by glioma stem cells that retain partial differentiation potential. Glioma stem cells are maintained in specialised microenvironments, but whether, or how, they undergo lineage progression outside of these niches remains unclear. Here we identify the white matter as a differentiative niche for glioblastomas with oligodendrocyte lineage competency. Tumour cells in contact with white matter acquire pre-oligodendrocyte fate, resulting in decreased proliferation and invasion. Differentiation is a response to white matter injury, which is caused by tumour infiltration itself in a tumoursuppressive feedback loop. Mechanistically, tumour cell differentiation is driven by selective white matter upregulation of SOX10, a master regulator of normal oligodendrogenesis. SOX10 overexpression or treatment with myelination-promoting agents that upregulate endogenous SOX10, mimic this response, leading to niche-independent pre-oligodendrocyte differentiation and tumour suppression in vivo. Thus, glioblastoma recapitulates an injury response and exploiting this latent programme may offer treatment opportunities for a subset of patients.


Assuntos
Neoplasias Encefálicas/patologia , Diferenciação Celular , Glioblastoma/patologia , Substância Branca/patologia , Animais , Neoplasias Encefálicas/ultraestrutura , Linhagem da Célula , Proliferação de Células , Progressão da Doença , Feminino , Regulação Neoplásica da Expressão Gênica , Glioblastoma/ultraestrutura , Camundongos Endogâmicos NOD , Camundongos SCID , Bainha de Mielina/metabolismo , Oligodendroglia/patologia , Fatores de Transcrição SOXE/metabolismo , Transcriptoma/genética , Regulação para Cima/genética
18.
Medicine (Baltimore) ; 100(16): e25603, 2021 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-33879726

RESUMO

ABSTRACT: Gliomas have the highest incidence among primary brain tumors, and the extracellular matrix (ECM) plays a vital role in tumor progression. We constructed a risk signature using ECM-related genes to predict the prognosis of patients with gliomas.mRNA and clinical data from glioma patients were downloaded from The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx) and Chinese Glioma Genome Atlas (CGGA) databases. Differentially expressed ECM-related genes were screened, and a risk signature was built using least absolute shrinkage and selection operator (LASSO) Cox regression. Cell type identification by estimating relative subsets of RNA transcripts (CIBERSORT) was used to assess immune infiltration in different risk groups. Gene set enrichment analysis (GSEA) was performed to explore the molecular mechanisms of the genes employed in the risk score.Differentially expressed ECM-related genes were identified, and their associated regulatory mechanisms were predicted via analysis of protein-protein interaction (PPI), transcription factor (TF) regulatory and TF coexpression networks. The established risk signature considered 17 ECM-related genes. The prognosis of the high-risk group was significantly worse than that of the low-risk group. We used the CGGA database to validate the signature. CIBERSORT indicated that the levels of naive B cells, activated memory CD4 T cells, regulatory T cells, gamma delta T cells, activated NK cells, monocytes, activated dendritic cells and activated mast cells were higher in the high-risk group. The levels of plasma cells, CD8 T cells, naive CD4 T cells, resting memory CD4 T cells, M0 macrophages, M1 macrophages, resting mast cells, and neutrophils were lower in the high-risk group. Ultimately, GSEA showed that the terms intestinal immune network for IgA production, primary immunodeficiency, and ECM receptor interaction were the top 3 terms enriched in the high-risk group. The terms Wnt signaling pathway, ErbB signaling pathway, mTOR signaling pathway, and calcium signaling pathway were enriched in the low-risk group.We built a risk signature to predict glioma prognosis using ECM-related genes. By evaluating immune infiltration and biofunctions, we gained a further understanding of this risk signature. This risk signature could be an effective tool for predicting glioma prognosis.This study did not require ethical approval. We will disseminate our findings by publishing results in a peer-reviewed journal.


Assuntos
Neoplasias Encefálicas/genética , Matriz Extracelular/genética , Glioma/genética , Medição de Risco/normas , Adulto , Biomarcadores Tumorais/genética , Neoplasias Encefálicas/mortalidade , Bases de Dados Genéticas , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica/genética , Glioma/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Modelos de Riscos Proporcionais , Mapas de Interação de Proteínas/genética , RNA Mensageiro/genética , Reprodutibilidade dos Testes , Fatores de Risco , Transdução de Sinais/genética , Fatores de Transcrição/genética
19.
Zhonghua Zhong Liu Za Zhi ; 43(4): 466-471, 2021 Apr 23.
Artigo em Chinês | MEDLINE | ID: mdl-33902209

RESUMO

Objective: To investigate the clinical value of magnetic resonance imaging (MRI) plain scan and diffusion weighted imaging (DWI) in the diagnosis of brain metastases. Methods: The MRI plain imaging findings of 105 cases with brain metastases and 103 cases without brain metastases confirmed by enhanced MRI examination and clinical diagnosis were retrospectively analyzed. The comparisons of plain MRI findings including T1 weighted image (T1WI), T2WI, T2/fluid attenuated inversion recovery (T2/FLAIR), DWI and apparent diffusion coefficient (ADC) values were made between brain metastases and non-brain metastases. Results: The numbers of hypo-intensity, iso-intensity, hyper-intensity and heterogeneous signal intensity of T1WI in the brain metastatic group were 54, 23, 9 and 19, respectively, while the numbers of hypo-intensity and iso-intensity in the non-brain metastatic group were 52 and 51, respectively, with statistically significant difference (P<0.001). The numbers of hypo-intensity, iso-intensity, hyper-intensity and heterogeneous signal intensity of T2WI in the brain metastatic group were 1, 9, 72 and 23, respectively, while the numbers of iso-intensity and hyper-intensity in the non-brain metastatic group were 11 and 92, respectively, with statistically significant difference (P<0.001). The numbers of hypo-intensity, hyper-intensity and heterogeneous signal intensity of DWI in the brain metastatic group were 4, 31 and 65, respectively, while the number of hyper-intensity in the non-brain metastatic group was 4 and others were iso-intensity, respectively, with statistically significant difference (P<0.001). The numbers of hypo-intensity, iso-intensity, hyper-intensity and heterogeneous signal intensity of T2WI/FLAIR in the brain metastatic group were 4, 5, 60 and 36, respectively, while all cases in the non-brain metastatic group were hyper-intensity, with statistically significant difference (P<0.001). The number of lesion accompanied with peripheral edema in the brain metastatic group were 69 cases, significantly higher than 0 cases in the non-brain metastatic group (P<0.001). The mean ADC value in the brain metastatic group were (0.919±0.019)×10(-3) mm(2)/s, significantly lower than (1.098±0.012)×10(-3) mm(2)/s of non-brain metastatic group (P<0.05). Conclusions: For patients with a history of primary malignancy, the MRI plain scan signals of T1WI, T2WI, T2WI/FLAIR and DWI are significantly different between brain metastatic tumor and non-metastatic tumor. The mixed signal, peripheral edema and the restriction of DWI diffusion indicate brain metastases. The combined application of the above parameters can improve the diagnostic efficacy of predicting brain metastases, and contrast enhancement MRI examination should be performed for the confirmation of diagnosis.


Assuntos
Neoplasias Encefálicas , Imagem de Difusão por Ressonância Magnética , Encéfalo/diagnóstico por imagem , Neoplasias Encefálicas/diagnóstico por imagem , Humanos , Imagem por Ressonância Magnética , Estudos Retrospectivos
20.
Br J Radiol ; 94(1121): 20201321, 2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-33876653

RESUMO

OBJECTIVE: This meta-analysis was carried out for assessing the accuracy of intravoxel incoherent motion (IVIM) parameters true diffusion coefficient (D), pseudo-diffusion coefficient (D*), and perfusion fraction (f) in differentiating low-grade gliomas (LGGs) from high-grade gliomas (HGGs). METHODS: Literatures concerning IVIM in the grading of brain gliomas published prior to October 20, 2020, searched in the Embase, PubMed, and Cochrane library. Use the quality assessment of diagnostic accuracy studies 2 (QUADAS 2) to evaluate the quality of studies. We estimated the pooled sensitivity, specificity, and the area under the summary ROC (SROC) curve to identification the accuracy of IVIM parameters D, D*, and f evaluation in grading gliomas. RESULTS: Totally, 6 articles including 252 brain gliomas conform to the inclusion criteria. The pooled sensitivity of parameters D, D*, and f derived from IVIM were 0.85 (95%Cl, 0.76-0.91), 0.78 (95%Cl, 0.71-0.85), and 0.89 (95%Cl, 0.76-0.96), respectively. The pooled specificity were 0.78 (95%Cl, 0.60-0.90), 0.68 (95%Cl, 0.56-0.79), and 0.88 (95%Cl, 0.76-0.94), respectively. Meanwhile, the AUC of SROC curve were 0.89 (95%Cl, 0.86-0.92) , 0.81 (95%Cl, 0.77-0.84), and 0.94 (95%Cl, 0.92-0.96), respectively. CONCLUSION: This meta-analysis suggested that IVIM parameters D, D*, and f have moderate or high diagnosis value accuracy in differentiating HGGs from LGGs, and the parameter f has greater sensitivity and specificity. Standardized methodology is warranted to guide the use of this method for clinical decision-making. However, more clinical studies are needed to prove our view. ADVANCES IN KNOWLEDGE: IVIM parameter f showed greater sensitivity and specificity, as well as excellent performance than parameter D* and D.


Assuntos
Neoplasias Encefálicas/diagnóstico por imagem , Glioma/diagnóstico por imagem , Imagem por Ressonância Magnética/métodos , Microcirculação , Área Sob a Curva , Neoplasias Encefálicas/irrigação sanguínea , Neoplasias Encefálicas/patologia , Intervalos de Confiança , Imagem de Difusão por Ressonância Magnética , Glioma/irrigação sanguínea , Glioma/patologia , Humanos , Gradação de Tumores , Razão de Chances , Viés de Publicação , Sensibilidade e Especificidade
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