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1.
Chinese Medical Journal ; (24): 394-407, 2024.
Article in English | WPRIM | ID: wpr-1007758

ABSTRACT

Gliomas tend to have a poor prognosis and are the most common primary malignant tumors of the central nervous system. Compared with patients with other cancers, glioma patients often suffer from increased levels of psychological stress, such as anxiety and fear. Chronic stress (CS) is thought to impact glioma profoundly. However, because of the complex mechanisms underlying CS and variability in individual tolerance, the role of CS in glioma remains unclear. This review suggests a new proposal to redivide the stress system into two parts. Neuronal activity is dominant upstream. Stress-signaling molecules produced by the neuroendocrine system are dominant downstream. We discuss the underlying molecular mechanisms by which CS impacts glioma. Potential pharmacological treatments are also summarized from the therapeutic perspective of CS.


Subject(s)
Humans , Glioma/pathology , Signal Transduction , Risk Factors , Anxiety , Brain Neoplasms/pathology
2.
Rev. neuro-psiquiatr. (Impr.) ; 86(1): 68-76, ene. 2023. tab, ilus
Article in Spanish | LILACS, LIPECS | ID: biblio-1442086

ABSTRACT

Objetivo: El presente artículo describe las características clínicas e imagenológicas de seis pacientes en edad pediátrica con diagnóstico de tumor cerebral atendidos en dos instituciones privadas de Lima durante la pandemia del COVID-19. Material y métodos: Estudio descriptivo de casos de tumor cerebral en pacientes menores de 18 años, atendidos en dos clínicas privadas de Lima, desde marzo 2020 a diciembre 2021. Resultados: Seis casos consecutivos de tumores intracraneales fueron detectados durante la mayor parte del primer año de la pandemia COVID-19 (periodo de octubre del 2020 a marzo del 2021), todos ellos con el diagnóstico de sarcoma intracraneal primario. Antes de la pandemia, el último sarcoma intracraneal primario en niños operado en las instituciones mencionadas ocurrió en junio del 2018 y fue el único caso de este tipo de tumor en el año. Conclusiones: Durante la pandemia de COVID-19, se encontró una inusual frecuencia de sarcoma intracraneal primario en niños en dos instituciones privadas de Lima.


SUMMARY Objective: The article describes the clinical and neuroimaging characteristics of six children with the diagnosis of brain tumor attended in two private institutions from Lima, during the COVID-19 pandemic. Material and methods: Descriptive study of cases of brain tumor in patients aged 18 and younger, followed at two private institutions in in Lima, from March 2020 to December 2021. Results: Six consecutive cases of intracranial tumors were detected during a large part of the COVID-19 pandemic's first year (October 2020 to March 2021), all of them with diagnosis of primary intracranial sarcoma. Before the pandemic, the last primary intracranial sarcoma in children, operated in the mentioned institutions, occurred in June 2018 and was the only case that year. Conclusions: During the COVID-19 pandemic, an unusual frequency of primary intracranial sarcoma in children was found in two private institutions from Lima.


Subject(s)
Humans , Child , Pediatrics , Sarcoma , Brain Neoplasms , Case Reports , Central Nervous System , Patients , COVID-19
3.
Chinese Journal of Pathology ; (12): 376-383, 2023.
Article in Chinese | WPRIM | ID: wpr-985683

ABSTRACT

Objective: To investigate the clinicopathological characteristics, pathological diagnosis and prognosis of diffuse midline glioma (DMG) with H3K27 alteration in adults. Methods: Twenty cases of H3K27-altered adult DMG diagnosed in the First Affiliated Hospital of Nanjing Medical University were enrolled from 2017 to 2022. All cases were evaluated by clinical and imaging presentations, HE, immunohistochemical staining and molecular genetics; and the relevant literature was reviewed. Results: The ratio of male to female was 1∶1, and the median age was 53 years (range from 25 to 74 years); the tumors were located in the brainstem (3/20, 15%) and non-brainstem (17/20, 85%; three in thoracolumbar spinal cord and one in pineal region). The clinical manifestations were non-specific, mostly dizziness, headache, blurred vision, memory loss, low back pain, limb sensation and/or movement disorders, etc. Microscopically, the tumors showed infiltrative growth, with WHO grade 2 (3 cases), grade 3 (12 cases), and grade 4 (5 cases). The tumors showed astrocytoma-like and oligdendroglioma-like, pilocytic astrocytoma-like and epithelioid-like patterns. Immunohistochemically, the tumor cells were positive for GFAP, Olig2 and H3K27M, and H3K27me3 expression was variably lost. ATRX expression was lost in four cases, p53 was strongly positive in 11 cases. Ki-67 index was about 5%-70%. Molecular genetics showed p. k27m mutation in exon 1 of H3F3A gene in 20 cases; BRAF mutation in two cases: V600E and L597Q mutation in one case each. Follow up intervals ranged from 1 to 58 months, and the survival time for brainstem (6.0 months) and non-brainstem (30.4 months) tumors was significantly different (P<0.05). Conclusions: DMG with H3K27 alteration is uncommonly found in adults, mostly occurs in non-brainstem, and can present in adults of all ages. Owing to the wide histomorphologic features, mainly astrocytic differentiation, routine detection of H3K27me3 in midline glioma is recommended. Molecular testing should be performed on any suspected cases to avoid missed diagnosis. Concomitant BRAF L597Q mutation and PPM1D mutation are novel findings. The overall prognosis of this tumor is poor, with tumors located in the brainstem showing worse outcome.


Subject(s)
Humans , Adult , Male , Female , Middle Aged , Aged , Histones/genetics , Brain Neoplasms/pathology , Proto-Oncogene Proteins B-raf/metabolism , Glioma/pathology , Astrocytoma/pathology , Mutation
4.
Frontiers of Medicine ; (4): 240-262, 2023.
Article in English | WPRIM | ID: wpr-982569

ABSTRACT

Detailed characterizations of genomic alterations have not identified subtype-specific vulnerabilities in adult gliomas. Mapping gliomas into developmental programs may uncover new vulnerabilities that are not strictly related to genomic alterations. After identifying conserved gene modules co-expressed with EGFR or PDGFRA (EM or PM), we recently proposed an EM/PM classification scheme for adult gliomas in a histological subtype- and grade-independent manner. By using cohorts of bulk samples, paired primary and recurrent samples, multi-region samples from the same glioma, single-cell RNA-seq samples, and clinical samples, we here demonstrate the temporal and spatial stability of the EM and PM subtypes. The EM and PM subtypes, which progress in a subtype-specific mode, are robustly maintained in paired longitudinal samples. Elevated activities of cell proliferation, genomic instability and microenvironment, rather than subtype switching, mark recurrent gliomas. Within individual gliomas, the EM/PM subtype was preserved across regions and single cells. Malignant cells in the EM and PM gliomas were correlated to neural stem cell and oligodendrocyte progenitor cell compartment, respectively. Thus, while genetic makeup may change during progression and/or within different tumor areas, adult gliomas evolve within a neurodevelopmental framework of the EM and PM molecular subtypes. The dysregulated developmental pathways embedded in these molecular subtypes may contain subtype-specific vulnerabilities.


Subject(s)
Humans , Brain Neoplasms/pathology , Neoplasm Recurrence, Local/metabolism , Glioma/pathology , Neural Stem Cells/pathology , Oligodendrocyte Precursor Cells/pathology , Tumor Microenvironment
5.
Journal of Zhejiang University. Science. B ; (12): 326-335, 2023.
Article in English | WPRIM | ID: wpr-982371

ABSTRACT

Neurosurgery is a highly specialized field: it often involves surgical manipulation of noble structures and cerebral retraction is frequently necessary to reach deep-seated brain lesions. There are still no reliable methods preventing possible retraction complications. The objective of this study was to design work chambers well suited for transcranial endoscopic surgery while providing safe retraction of the surrounding brain tissue. The chamber is designed to be inserted close to the intracranial point of interest; once it is best placed it can be opened. This should guarantee an appreciable workspace similar to that of current neurosurgical procedures. The experimental aspect of this study involved the use of a force sensor to evaluate the pressures exerted on the brain tissue during the retraction phase. Following pterional craniotomy, pressure measurements were made during retraction with the use of a conventional metal spatula with different inclinations. Note that, although the force values necessary for retraction and exerted on the spatula by the neurosurgeon are the same, the local pressure exerted on the parenchyma at the edge of the spatula at different inclinations varied greatly. A new method of cerebral retraction using a chamber retractor (CR) has been designed to avoid any type of complication due to spatula edge overpressures and to maintain acceptable pressure values exerted on the parenchyma.


Subject(s)
Humans , Brain/surgery , Neurosurgical Procedures/methods , Neurosurgery , Brain Neoplasms , Endoscopy
6.
Chinese Journal of Lung Cancer ; (12): 400-406, 2023.
Article in Chinese | WPRIM | ID: wpr-982172

ABSTRACT

Lung cancer is one of the most lethal malignancies in the world, with non-small cell lung cancer (NSCLC) accounting for approximately 80%-85% of all pathological types. Approximately 30%-55% of NSCLC patients develop brain metastases. It has been reported that 5%-6% of patients with brain metastases harbor anaplastic lymphoma kinase (ALK) fusion. ALK-positive NSCLC patients have shown significant therapeutic benefits after treatment with ALK inhibitors. Over the past decade, ALK inhibitors have rapidly evolved and now exist in three generations: first-generation drugs such as Crizotinib; second-generation drugs including Alectinib, Brigatinib, Ceritinib, and Ensartinib; and third-generation drugs like Lorlatinib. These drugs have exhibited varying efficacy in treating brain metastases in ALK-positive NSCLC patients. However, the numerous options available for ALK inhibition present a challenge for clinical decision-making. Therefore, this review aims to provide clinical guidance by summarizing the efficacy and safety of ALK inhibitors in treating NSCLC brain metastases.
.


Subject(s)
Humans , Carcinoma, Non-Small-Cell Lung/drug therapy , Lung Neoplasms/drug therapy , Brain Neoplasms/drug therapy , Protein Kinase Inhibitors/adverse effects , Crizotinib
7.
Ann. afr. méd. (En ligne) ; 16(2): 5058-5066, 2023. tables
Article in French | AIM | ID: biblio-1425738

ABSTRACT

Contexte et objectif. Malgré leur fréquence élevée, très peu d'études ont été menées sur les tumeurs bénignes du sein (TBS) en Afrique subsaharienne. L'objectif de la présente étude a été d'évaluer la valeur diagnostique des explorations clinique et échographique mammaire des TBS en milieu peu équipé. Méthodes. Il s'agissait d'une étude documentaire, sur les TBS suivies aux Cliniques Universitaires de Kinshasa, entre janvier 2016 et décembre 2021. La valeur diagnostique des explorations clinique et échographique mammaire des TBS (sensibilité, spécificité, valeur prédictive négative VPN, VPP, coefficient Kappa) a été calculée en prenant pour référence la découverte anatomopathologique des pièces biopsiques. Résultats. Au total, 81 dossiers de TBS ont été colligés. Le Fibroadénome 58 (71,6 %), la Maladie fibrokystique (MFK) 15 (18,5 %), l'Adénome tubuleux 6(7,4 %), la Tumeur Phyllode (TP) 1(1,2 %) et le kyste 1(1,2 %) étaient les tumeurs diagnostiquées à l'anatomopathologie, après tumorectomies. A l'examen clinique, la capacité diagnostique des TBS autres que le Fibroadénome était nulle. La spécificité, la VPN et le coefficient kappa étaient respectivement, de 60,0 %, 39,1 % et 32,2 % pour le diagnostic du Fibroadénome. L'échographie mammaire était faite dans 98,6 % tandis que la mammographie seulement dans 11,1 % des cas. La majorité des tumeurs étaient classées Breast Imaging reporting and Data system (BIRADS) 2 (70,0 %). La spécificité, la VPN et le coefficient kappa étaient respectivement, de 80,6 %, 40,9 % et 39,0 % pour le Fibroadénome, et de 84,4 %, 66,7 % et 1,9 % pour la MFK. La TP était classée BIRADS3. Conclusion. L'échographie mammaire très réalisée, est très performante dans la classification BIRADS des TBS; les cliniciens exerçant en milieu peu équipé peuvent donc sans équivoque suivre les recommandations sur la prise en charge des tumeurs classées BIRADS2 et BIRADS3 à l'échographie, bien que sa performance en ce qui concerne le diagnostic différentiel de ces tumeurs soit moindre.


Subject(s)
Humans , Brain Neoplasms , Breast Diseases , Diagnostic Services , Breast Neoplasms , Ultrasonography, Mammary , Medical Laboratory Personnel
8.
Rev. Bras. Cancerol. (Online) ; 69(4): e-054051, out-dez. 2023.
Article in Spanish, Portuguese | LILACS, SES-SP | ID: biblio-1523382

ABSTRACT

Introdução: As neoplasias de sistema nervoso central representam 21% do câncer infantojuvenil, sendo a principal causa de morte nessa população em países desenvolvidos. Avanços na neuroimagem têm melhorado seu diagnóstico, e a combinação de terapias tem permitido a cura, com maior preservação neurológica. A cirurgia é o principal tratamento, frequentemente combinada com radioterapia e quimioterapia. Objetivo: Descrever achados socioeconômicos, sinais e sintomas, e aspectos histológicos dos tumores cerebrais pediátricos, tratados com radioterapia. Método: Estudo transversal e descritivo, utilizando prontuários de 257 crianças e adolescentes portadores de neoplasias de sistema nervoso central, tratados com radioterapia no Instituto Nacional de Câncer, no Rio de Janeiro, de 2012 a 2020. As variáveis foram divididas em sociodemográficas, clínicas e patológicas. Resultados: Crianças brancas do sexo masculino foram as mais prevalentes, com mediana de idade de 7,5 anos no diagnóstico e de 8,0 anos na radioterapia. A maioria possuía casa própria com infraestrutura básica e renda familiar de até um salário-mínimo. Os sintomas mais comuns foram cefaleia, vômitos e alterações na marcha, variando de acordo com a localização do tumor e a idade da criança. A radioterapia foi utilizada em 64% dos pacientes, principalmente para meduloblastoma, tumores de tronco cerebral e ependimoma anaplásico. Conclusão: Estudos específicos sobre crianças e adolescentes com neoplasias cerebrais tratados com radioterapia são raros na literatura. Quando comparados com a população em geral, apresentam perfis sociodemográficos e clínicos semelhantes, com diferenças notáveis apenas na frequência dos tipos tumorais


Introduction: Central nervous system neoplasms account for 21% of pediatric cancer cases and are the leading cause of death in this population in developed countries. Advances in neuroimaging have improved diagnosis, and combination therapies have ensured the cure with greater neurological preservation. Surgery is the primary treatment, often combined with radiation therapy and chemotherapy. Objective: To describe socioeconomic findings, signs and symptoms, and histological aspects of pediatric brain tumors treated with radiation therapy. Method: A cross-sectional and descriptive study was conducted with 257 children and adolescents utilizing medical records with central nervous system neoplasms treated with radiotherapy at the National Cancer Institute, Rio de Janeiro, from 2012 to 2020. The variables were divided into sociodemographic, clinical, and pathological categories. Results: White male children were the most prevalent, with a median age at diagnosis of 7.5 years and at radiotherapy, of 8.0 years. The majority had their own home with basic infrastructure and family income of up to one minimum wage. The most common symptoms were headache, vomiting, and gait disorders, varying according to tumor location and child's age. Radiation therapy was used in 64% of patients, mainly for medulloblastoma, brainstem tumors, and anaplastic ependymoma. Conclusion: Specific studies on children and adolescents with brain neoplasms treated with radiotherapy are rare in the literature. When compared with the general population, they present similar sociodemographic and clinical profiles, with remarkable differences only in the frequency of tumor types


Introducción: Las neoplasias del sistema nervioso central representan el 21% del cáncer infantil y juvenil, siendo la principal causa de muerte en esta población en países desarrollados. Los avances en neuroimagen han mejorado su diagnóstico y la combinación de terapias viene permitiendo la cura, con una mayor preservación neurológica. La cirugía es el tratamiento principal, a menudo combinada con radioterapia y quimioterapia. Objetivo: Describir los hallazgos socioeconómicos, los signos y síntomas, y los aspectos histológicos de los tumores cerebrales pediátricos tratados con radioterapia. Método: Estudio transversal y descriptivo utilizando las historias clínicas de 257 niños y adolescentes con neoplasias del sistema nervioso central, que fueron tratados con radioterapia en el Instituto Nacional del Cáncer en Río de Janeiro entre 2012 y 2020. Las variables se dividieron en sociodemográficas, clínicas y patológicas. Resultado: Los niños blancos y de sexo masculino fueron los más prevalentes, con una mediana de edad de 7,5 años en el momento del diagnóstico y de 8,0 años en el momento de la radioterapia. La mayoría poseía una vivienda propia con infraestructura básica y un ingreso familiar de hasta un salario mínimo. Los síntomas más comunes fueron dolor de cabeza, vómitos y alteraciones en la marcha, que variaban según la ubicación del tumor y la edad del niño. Se utilizó radioterapia en el 64% de los pacientes, principalmente para meduloblastoma, tumores del tronco cerebral y ependimoma anaplásico. Conclusión: Los estudios específicos sobre niños y adolescentes con neoplasias cerebrales tratados con radioterapia son raros en la literatura. Cuando se comparan con la población en general, presentan perfiles sociodemográficos y clínicos similares, con diferencias notables solo en la frecuencia de los tipos tumorales


Subject(s)
Humans , Male , Female , Child , Socioeconomic Factors , Brain Neoplasms , Cancer Care Facilities , Child , Epidemiology , Central Nervous System Neoplasms/radiotherapy , Age and Sex Distribution , Brazil
9.
Journal of Southern Medical University ; (12): 1071-1080, 2023.
Article in Chinese | WPRIM | ID: wpr-987024

ABSTRACT

OBJECTIVE@#To investigate the effect of lactic acid-induced upregulation of PLEKHA4 expression on biological behaviors of glioma cells and the possible molecular mechanism.@*METHODS@#GEO database and GEPIA2 website were used to analyze the relationship between PLEKHA4 expression level and the pathological grade of glioma. A specific PLEKHA4 siRNA was transfected in glioma U251 and T98G cells, and the changes in cell proliferation ability were assessed by real-time cell analysis technology and Edu experiment. The colony-forming ability of the cells was evaluated using plate cloning assay, and cell cycle changes and cell apoptosis were analyzed with flow cytometry. The mRNA expression of PLEKHA4 was detected by PCR in glioma samples and controls and in glioma cells treated with lactic acid and glucose. Xenograft mice in vivo was used to detect tumor formation in nude mice; Western blotting was used to detect the expressions of cyclinD1, CDK2, Bcl2, β-catenin and phosphorylation of the key proteins in the MAPK signaling pathway.@*RESULTS@#The results of GEO database and online website analysis showed that PLEKHA4 was highly expressed in glioma tissues and was associated with poor prognosis; PLEKHA4 knockdown obviously inhibited the proliferation and attenuated the clone-forming ability of the glioma cells (P < 0.05). Flow cytometry showed that PLEKHA4 knockdown caused cell cycle arrest in G1 phase and promoted apoptosis of the cells (P < 0.01). PLEKHA4 gene mRNA expression was increased in glioma samples and glioma cells after lactate and glucose treatment (P < 0.01). PLEKHA4 knockdown, tumor formation ability of nude mice decreased; PLEKHA4 knockdown obviously lowered the expression of cyclinD1, CDK2, Bcl2 and other functional proteins, inhibited the phosphorylation of ERK and p38 and reduced the expression of β-catenin protein (P < 0.01).@*CONCLUSION@#PLEKHA4 knockdown inhibited the proliferation of glioma cells and promoted apoptosis by inhibiting the activation of the MAPK signaling pathway and expression of β-catenin. Lactic acid produced by glycolysis upregulates the expression of PLEKHA4 in glioma cells.


Subject(s)
Humans , Animals , Mice , Up-Regulation , beta Catenin/metabolism , Mice, Nude , Brain Neoplasms/pathology , Lactic Acid , Cell Line, Tumor , Glioma/pathology , Cell Proliferation , Apoptosis , Proto-Oncogene Proteins c-bcl-2/metabolism , RNA, Messenger/genetics , Gene Expression Regulation, Neoplastic
10.
Chinese Journal of Surgery ; (12): 61-65, 2023.
Article in Chinese | WPRIM | ID: wpr-970174

ABSTRACT

Objective: To examine the application value of 3D Slicer software assisted domestic frameless stereotactic robot in biopsy of intracranial lesions. Methods: A retrospective analysis was performed on 80 patients who admitted consecutively and underwent intracerebral lesions biopsy with the domestic frameless stereotactic robot at Department of Neurosurgery, Aerospace Central Hospital from January 2019 to December 2021. There were 36 males and 44 females, with a mean age of (38.5±18.0) years (range: 6 to 71 years). Before surgery only enhanced T1-weighted three-dimensional magnetization prepared gradient echo sequences and diffusion tensor imaging scans were performed. Self-reconstruction of intracranial lesions, cerebral cortex and blood vessels was carried out using 3D Slicer software system after the DICOM format imaging data of 80 patients were collected. These imaging data were merged to the workstation of the domestic frameless stereotactic robot for preoperative surgical planning and the surgical puncture path was designed to avoid blood vessels in the brain functional area, cerebral cortex and sulcus. Results: All frameless stereotactic biopsy were successfully performed. Postoperative pathological diagnosis included 50 cases of diffuse astrocytic and oligodendroglioma, 15 cases of lymphoma, 5 cases of metastatic tumors, 5 cases of inflammatory demyelinating disease, 2 cases of inflammatory granuloma, 1 case of hemangioma, 1 case of acute lymphoblastic leukemia intracranial invasion and 1 case of seminoma. The positive diagnosis rate was 100% (80/80). Postoperative imaging confirmed that the puncture path and target were accurately implemented according to the preoperative planning, and the target error was (1.32±0.44) mm (range: 0.55 to 1.99 mm). One case of puncture-related bleeding occurred at the target after surgery and improved after treatment. Conclusion: The three-dimensional multimodal images reconstructed by the 3D Slicer software before operation could help the surgeons make the preoperative planning and reduce the risk of stereotactic brain biopsy.


Subject(s)
Male , Female , Humans , Child , Adolescent , Young Adult , Adult , Middle Aged , Aged , Brain Neoplasms/pathology , Diffusion Tensor Imaging , Retrospective Studies , Robotics , Biopsy , Software , Stereotaxic Techniques
11.
Chinese Medical Journal ; (24): 2551-2561, 2023.
Article in English | WPRIM | ID: wpr-1007566

ABSTRACT

BACKGROUND@#The brain is a common metastatic site in patients with non-small cell lung cancer (NSCLC), resulting in a relatively poor prognosis. Systemic therapy with epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) is recommended as the first-line treatment for EGFR -mutated, advanced NSCLC patients. However, intracranial activity varies in different drugs. Thus, brain metastasis (BM) should be considered when choosing the treatment regimens. We conducted this network meta-analysis to explore the optimal first-line therapeutic schedule for advanced EGFR -mutated NSCLC patients with different BM statuses.@*METHODS@#Randomized controlled trials focusing on EGFR-TKIs (alone or in combination) in advanced and EGFR -mutant NSCLC patients, who have not received systematic treatment, were systematically searched up to December 2021. We extracted and analyzed progression-free survival (PFS) and overall survival (OS). A network meta-analysis was performed with the Bayesian statistical model to determine the survival outcomes of all included therapy regimens using the R software. Hazard ratios (HRs) and 95% confidence intervals (CIs) were used to compare intervention measures, and overall rankings of therapies were estimated under the Bayesian framework.@*RESULTS@#This analysis included 17 RCTs with 5077 patients and 12 therapies, including osimertinib + bevacizumab, aumolertinib, osimertinib, afatinib, dacomitinib, standards of care (SoC, including gefitinib, erlotinib, or icotinib), SoC + apatinib, SoC + bevacizumab, SoC + ramucirumab, SoC + pemetrexed based chemotherapy (PbCT), PbCT, and pemetrexed free chemotherapy (PfCT). For patients with BM, SoC + PbCT improved PFS compared with SoC (HR = 0.40, 95% CI: 0.17-0.95), and osimertinib + bevacizumab was most likely to rank first in PFS, with a cumulative probability of 34.5%, followed by aumolertinib, with a cumulative probability of 28.3%. For patients without BM, osimertinib + bevacizumab, osimertinib, aumolertinib, SoC + PbCT, dacomitinib, SoC + ramucirumab, SoC + bevacizumab, and afatinib showed superior efficacy compared with SoC (HR = 0.43, 95% CI: 0.20-0.90; HR = 0.46, 95% CI: 0.31-0.68; HR = 0.51, 95% CI: 0.34-0.77; HR = 0.50, 95% CI: 0.38-0.66; HR = 0.62, 95% CI: 0.43-0.89; HR = 0.64, 95% CI: 0.44-0.94; HR = 0.61, 95% CI: 0.48-0.76; HR = 0.71, 95% CI: 0.50-1.00), PbCT (HR = 0.29, 95% CI: 0.11-0.74; HR = 0.31, 95% CI: 0.15-0.62; HR = 0.34, 95% CI: 0.17-0.69; HR = 0.34, 95% CI: 0.18-0.64; HR = 0.42, 95% CI: 0.21-0.82; HR = 0.43, 95% CI: 0.22-0.87; HR = 0.41, 95% CI: 0.22-0.74; HR = 0.48, 95% CI: 0.31-0.75), and PfCT (HR = 0.14, 95% CI: 0.06-0.32; HR = 0.15, 95% CI: 0.09-0.26; HR = 0.17, 95% CI: 0.09-0.29; HR = 0.16, 95% CI: 0.10-0.26; HR = 0.20, 95% CI: 0.12-0.35; HR = 0.21, 95% CI: 0.12-0.39; HR = 0.20, 95% CI: 0.12-0.31; HR = 0.23, 95% CI: 0.16-0.34) in terms of PFS. And, SoC + apatinib showed relatively superior PFS when compared with PbCT (HR = 0.44, 95% CI: 0.22-0.92) and PfCT (HR = 0.21, 95% CI: 0.12-0.39), but similar PFS to SoC (HR = 0.65, 95% CI: 0.42-1.03). No statistical differences were observed for PFS in patients without BM between PbCT and SoC (HR = 1.49, 95% CI: 0.84-2.64), but both showed favorable PFS when compared with PfCT (PfCT vs. SoC, HR = 3.09, 95% CI: 2.06-4.55; PbCT vs. PfCT, HR = 0.14, 95% CI: 0.06-0.32). For patients without BM, osimertinib + bevacizumab was most likely to rank the first, with cumulative probabilities of 47.1%. For OS, SoC + PbCT was most likely to rank first in patients with and without BM, with cumulative probabilities of 46.8%, and 37.3%, respectively.@*CONCLUSION@#Osimertinib + bevacizumab is most likely to rank first in PFS in advanced EGFR -mutated NSCLC patients with or without BM, and SoC + PbCT is most likely to rank first in OS.


Subject(s)
Humans , Carcinoma, Non-Small-Cell Lung/metabolism , Afatinib/therapeutic use , Lung Neoplasms/metabolism , Bevacizumab/therapeutic use , Bayes Theorem , Network Meta-Analysis , Protein Kinase Inhibitors/therapeutic use , Pemetrexed/therapeutic use , ErbB Receptors/genetics , Brain Neoplasms/genetics , Mutation/genetics
12.
Neuroscience Bulletin ; (6): 1873-1886, 2023.
Article in English | WPRIM | ID: wpr-1010659

ABSTRACT

The increasing number of long-term survivors of pediatric brain tumors requires us to incorporate the most recent knowledge derived from cognitive neuroscience into their oncological treatment. As the lesion itself, as well as each treatment, can cause specific neural damage, the long-term neurocognitive outcomes are highly complex and challenging to assess. The number of neurocognitive studies in this population grows exponentially worldwide, motivating modern neuroscience to provide guidance in follow-up before, during and after treatment. In this review, we provide an overview of structural and functional brain connectomes and their role in the neuropsychological outcomes of specific brain tumor types. Based on this information, we propose a theoretical neuroscientific framework to apply appropriate neuropsychological and imaging follow-up for future clinical care and rehabilitation trials.


Subject(s)
Child , Humans , Brain/diagnostic imaging , Brain Neoplasms/complications , Cognitive Dysfunction , Connectome , Neurosciences
13.
Journal of Zhejiang University. Science. B ; (12): 698-710, 2023.
Article in English | WPRIM | ID: wpr-1010564

ABSTRACT

To explore the role of forkhead box protein O1 (FOXO1) in the progression of glioblastoma multiforme (GBM) and related drug resistance, we deciphered the roles of FOXO1 and miR-506 in proliferation, apoptosis, migration, invasion, autophagy, and temozolomide (TMZ) sensitivity in the U251 cell line using in vitro and in vivo experiments. Cell viability was tested by a cell counting kit-8 (CCK8) kit; migration and invasion were checked by the scratching assay; apoptosis was evaluated by terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) staining and flow cytometry. The construction of plasmids and dual-luciferase reporter experiment were carried out to find the interaction site between FOXO1 and miR-506. Immunohistochemistry was done to check the protein level in tumors after the in vivo experiment. We found that the FOXO1-miR-506 axis suppresses GBM cell invasion and migration and promotes GBM chemosensitivity to TMZ, which was mediated by autophagy. FOXO1 upregulates miR-506 by binding to its promoter to enhance transcriptional activation. MiR-506 could downregulate E26 transformation-specific 1 (ETS1) expression by targeting its 3'-untranslated region (UTR). Interestingly, ETS1 promoted FOXO1 translocation from the nucleus to the cytosol and further suppressed the FOXO1-miR-506 axis in GBM cells. Consistently, both miR-506 inhibition and ETS1 overexpression could rescue FOXO1 overactivation-mediated TMZ chemosensitivity in mouse models. Our study demonstrated a negative feedback loop of FOXO1/miR-506/ETS1/FOXO1 in GBM in regulating invasiveness and chemosensitivity. Thus, the above axis might be a promising therapeutic target for GBM.


Subject(s)
Animals , Mice , Humans , Brain Neoplasms/genetics , Cell Line, Tumor , Cell Proliferation , Drug Resistance, Neoplasm , Feedback , Gene Expression Regulation, Neoplastic , Glioblastoma/metabolism , MicroRNAs/metabolism , Temozolomide/therapeutic use , Forkhead Box Protein O1/metabolism
14.
Journal of Biomedical Engineering ; (6): 482-491, 2023.
Article in Chinese | WPRIM | ID: wpr-981566

ABSTRACT

Recently, deep learning has achieved impressive results in medical image tasks. However, this method usually requires large-scale annotated data, and medical images are expensive to annotate, so it is a challenge to learn efficiently from the limited annotated data. Currently, the two commonly used methods are transfer learning and self-supervised learning. However, these two methods have been little studied in multimodal medical images, so this study proposes a contrastive learning method for multimodal medical images. The method takes images of different modalities of the same patient as positive samples, which effectively increases the number of positive samples in the training process and helps the model to fully learn the similarities and differences of lesions on images of different modalities, thus improving the model's understanding of medical images and diagnostic accuracy. The commonly used data augmentation methods are not suitable for multimodal images, so this paper proposes a domain adaptive denormalization method to transform the source domain images with the help of statistical information of the target domain. In this study, the method is validated with two different multimodal medical image classification tasks: in the microvascular infiltration recognition task, the method achieves an accuracy of (74.79 ± 0.74)% and an F1 score of (78.37 ± 1.94)%, which are improved as compared with other conventional learning methods; for the brain tumor pathology grading task, the method also achieves significant improvements. The results show that the method achieves good results on multimodal medical images and can provide a reference solution for pre-training multimodal medical images.


Subject(s)
Humans , Algorithms , Brain/diagnostic imaging , Brain Neoplasms/diagnostic imaging , Recognition, Psychology
15.
Chinese Journal of Biotechnology ; (12): 1477-1501, 2023.
Article in Chinese | WPRIM | ID: wpr-981149

ABSTRACT

Patients with glioblastoma (GBM) generally have a bad prognosis and short overall survival after being treated with surgery, chemotherapy or radiotherapy due to the histological heterogeneity, strong invasive ability and rapid postoperative recurrence of GBM. The components of GBM cell-derived exosome (GBM-exo) can regulate the proliferation and migration of GBM cell via cytokines, miRNAs, DNA molecules and proteins, promote the angiogenesis via angiogenic proteins and non-coding RNAs, mediate tumor immune evasion by targeting immune checkpoints with regulatory factors, proteins and drugs, and reduce drug resistance of GBM cells through non-coding RNAs. GBM-exo is expected to be an important target for the personalized treatment of GBM and a marker for diagnosis and prognosis of this kind of disease. This review summarizes the preparation methods, biological characteristics, functions and molecular mechanisms of GBM-exo on cell proliferation, angiogenesis, immune evasion and drug resistance of GBM to facilitate developing new strategies for the diagnosis and treatment of GBM.


Subject(s)
Humans , Glioblastoma/genetics , Exosomes/metabolism , MicroRNAs/metabolism , Prognosis , Cell Proliferation , Brain Neoplasms/genetics , Cell Line, Tumor
16.
Chinese Medical Journal ; (24): 1699-1707, 2023.
Article in English | WPRIM | ID: wpr-980954

ABSTRACT

BACKGROUND@#Breast cancer is one of the most common cancer in women and a proportion of patients experiences brain metastases with poor prognosis. The study aimed to construct a novel predictive clinical model to evaluate the overall survival (OS) of patients with postoperative brain metastasis of breast cancer (BCBM) and validate its effectiveness.@*METHODS@#From 2010 to 2020, a total of 310 female patients with BCBM were diagnosed in The Affiliated Cancer Hospital of Xinjiang Medical University, and they were randomly assigned to the training cohort and the validation cohort. Data of another 173 BCBM patients were collected from the Surveillance, Epidemiology, and End Results Program (SEER) database as an external validation cohort. In the training cohort, the least absolute shrinkage and selection operator (LASSO) Cox regression model was used to determine the fundamental clinical predictive indicators and the nomogram was constructed to predict OS. The model capability was assessed using receiver operating characteristic, C-index, and calibration curves. Kaplan-Meier survival analysis was performed to evaluate clinical effectiveness of the risk stratification system in the model. The accuracy and prediction capability of the model were verified using the validation and SEER cohorts.@*RESULTS@#LASSO Cox regression analysis revealed that lymph node metastasis, molecular subtype, tumor size, chemotherapy, radiotherapy, and lung metastasis were statistically significantly correlated with BCBM. The C-indexes of the survival nomogram in the training, validation, and SEER cohorts were 0.714, 0.710, and 0.670, respectively, which showed good prediction capability. The calibration curves demonstrated that the nomogram had great forecast precision, and a dynamic diagram was drawn to increase the maneuverability of the results. The Risk Stratification System showed that the OS of low-risk patients was considerably better than that of high-risk patients ( P < 0.001).@*CONCLUSION@#The nomogram prediction model constructed in this study has a good predictive value, which can effectively evaluate the survival rate of patients with postoperative BCBM.


Subject(s)
Female , Humans , Breast Neoplasms/surgery , Retrospective Studies , Prognosis , Brain Neoplasms/surgery , Nomograms
17.
Chinese Medical Journal ; (24): 1422-1429, 2023.
Article in English | WPRIM | ID: wpr-980945

ABSTRACT

BACKGROUND@#Immune checkpoint inhibitors (ICIs) are increasingly used as first-line therapy for patients with advanced non-small cell lung cancer (NSCLC) harboring no actionable mutations; however, data on their efficacy among patients presenting with intracranial lesions are limited. This study aimed to explore the efficacy and safety of ICIs combined with chemotherapy in advanced NSCLC patients with measurable brain metastasis at initial diagnosis.@*METHODS@#Our study retrospectively analyzed clinical data of a total of 211 patients diagnosed with driver gene mutation-negative advanced NSCLC with measurable, asymptomatic brain metastasis at baseline from Hunan Cancer Hospital between January 1, 2019 and September 30, 2021. The patients were stratified into two groups according to the first-line treatment regimen received: ICI combined with chemotherapy ( n = 102) or chemotherapy ( n = 109). Systemic and intracranial objective response rates (ORRs) and progression-free survival (PFS) were analyzed. Adverse events were also compared between the groups.@*RESULTS@#Compared with the chemotherapy-based regimen, the ICI-containing regimen was associated with a significantly higher intracranial (44.1% [45/102] vs . 28.4% [31/109], χ2 = 5.620, P = 0.013) and systemic (49.0% [50/102] vs . 33.9% [37/109], χ2 = 4.942, P = 0.019) ORRs and longer intracranial (11.0 months vs . 7.0 months, P <0.001) and systemic (9.0 months vs . 5.0 months, P <0.001) PFS. Multivariable analysis consistently revealed an independent association between receiving ICI plus platinum-based chemotherapy as a first-line regimen and prolonged intracranial PFS (hazard ratio [HR] = 0.52, 95% confidence interval [CI]: 0.37-0.73, P <0.001) and systemic PFS (HR = 0.48, 95% CI: 0.35-0.66, P <0.001). No unexpected serious adverse effects were observed.@*CONCLUSION@#Our study provides real-world clinical evidence that ICI combined with chemotherapy is a promising first-line treatment option for driver gene mutation-negative advanced NSCLC patients who present with brain metastasis at initial diagnosis.@*CLINICAL TRIAL REGISTRATION@#https://www.clinicaltrials.gov/ , OMESIA, NCT05129202.


Subject(s)
Humans , Carcinoma, Non-Small-Cell Lung/genetics , Lung Neoplasms/genetics , Immune Checkpoint Inhibitors/therapeutic use , Retrospective Studies , Brain Neoplasms/genetics
18.
Chinese Medical Journal ; (24): 1523-1531, 2023.
Article in English | WPRIM | ID: wpr-980918

ABSTRACT

Lung cancer has the highest risk of brain metastasis (BM) among all solid carcinomas. The emergence of BM has a significant impact on the selection of oncologic treatment for patients. Immune checkpoint inhibitors (ICIs) are the most promising treatment option for patients without druggable mutations and have been shown to improve survival in patients with non-small cell lung cancer (NSCLC) BM in clinical trials with good safety. Moreover, ICI has shown certain effects in NSCLC BM, and the overall intracranial efficacy is comparable to extracranial efficacy. However, a proportion of patients showed discordant responses in primary and metastatic lesions, suggesting that multiple mechanisms may exist underlying ICI activity in BM. According to studies pertaining to tumor immune microenvironments, ICIs may be capable of provoking immunity in situ . Meanwhile, systematic immune cells activated by ICIs can migrate into the central nervous system and exert antitumor effects. This review summarizes the present evidence for ICI treatment efficacy in NSCLC BM and proposes the possible mechanisms of ICI treatment for NSCLC BMs based on existing evidence.


Subject(s)
Humans , Carcinoma, Non-Small-Cell Lung/drug therapy , Lung Neoplasms/drug therapy , Immune Checkpoint Inhibitors/therapeutic use , Brain Neoplasms/drug therapy , Carcinoma , Tumor Microenvironment
19.
Chinese Medical Journal ; (24): 780-787, 2023.
Article in English | WPRIM | ID: wpr-980829

ABSTRACT

Magnetic resonance-guided focused ultrasound (MRgFUS) is a novel and minimally invasive technology. Since the US Food and Drug Administration approved unilateral ventral intermediate nucleus-MRgFUS for medication-refractory essential tremor in 2016, studies on new indications, such as Parkinson's disease (PD), psychiatric diseases, and brain tumors, have been on the rise, and MRgFUS has become a promising method to treat such neurological diseases. Currently, as the second most common degenerative disease, PD is a research hotspot in the field of MRgFUS. The actions of MRgFUS on the brain range from thermoablation, blood-brain barrier (BBB) opening, to neuromodulation. Intensity is a key determinant of ultrasound actions. Generally, high intensity can be used to precisely thermoablate brain targets, whereas low intensity can be used as molecular therapies to modulate neuronal activity and open the BBB in conjunction with injected microbubbles. Here, we aimed to summarize advances in the application of MRgFUS for the treatment of PD, with a focus on thermal ablation, BBB opening, and neuromodulation, in the hope of informing clinicians of current applications.


Subject(s)
Humans , Parkinson Disease/therapy , Brain , Blood-Brain Barrier , Essential Tremor/surgery , Brain Neoplasms , Magnetic Resonance Imaging/methods , Magnetic Resonance Spectroscopy
20.
Journal of Integrative Medicine ; (12): 120-129, 2023.
Article in English | WPRIM | ID: wpr-971656

ABSTRACT

Globally, it is evident that glioblastoma multiforme (GBM) is an aggressive malignant cancer with a high mortality rate and no effective treatment options. Glioblastoma is classified as the stage-four progression of a glioma tumor, and its diagnosis results in a shortened life expectancy. Treatment options for GBM include chemotherapy, immunotherapy, surgical intervention, and conventional pharmacotherapy; however, at best, they extend the patient's life by a maximum of 5 years. GBMs are considered incurable due to their high recurrence rate, despite various aggressive therapeutic approaches which can have many serious adverse effects. Ceramides, classified as endocannabinoids, offer a promising novel therapeutic approach for GBM. Endocannabinoids may enhance the apoptosis of GBM cells but have no effect on normal healthy neural cells. Cannabinoids promote atypical protein kinase C, deactivate fatty acid amide hydrolase enzymes, and activate transient receptor potential vanilloid 1 (TRPV1) and TRPV2 to induce pro-apoptotic signaling pathways without increasing endogenous cannabinoids. In previous in vivo studies, endocannabinoids, chemically classified as amide formations of oleic and palmitic acids, have been shown to increase the pro-apoptotic activity of human cancer cells and inhibit cell migration and angiogenesis. This review focuses on the biological synthesis and pharmacology of endogenous cannabinoids for the enhancement of cancer cell apoptosis, which have potential as a novel therapy for GBM. Please cite this article as: Duzan A, Reinken D, McGomery TL, Ferencz N, Plummer JM, Basti MM. Endocannabinoids are potential inhibitors of glioblastoma multiforme proliferation. J Integr Med. 2023; 21(2): 120-128.


Subject(s)
Humans , Glioblastoma/pathology , Endocannabinoids/therapeutic use , Brain Neoplasms/pathology , Cell Proliferation , Cell Line, Tumor , Cannabinoids/therapeutic use
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