Radionecrosis cerebral en un adulto

Se presenta el caso clínico de un paciente de 37 años de edad con el antecedente de haber recibido radioterapia por una lesión tumoral en la región frontal derecha, el cual acudió a consulta en el Instituto de Neurología y Neurocirugía de Cuba por presentar cefalea intensa y hemiparesia izquierda. Luego de realizados los exámenes necesarios, se estableció el diagnóstico clínico-imagenológico de lesión por radionecrosis en el hemisferio contralateral, que fue corroborado en el estudio anatomopatológico una vez que se extirpó el tumor; seguidamente, se indicó inmunoterapia. La evolución del paciente fue satisfactoria, pues se logró el control de la enfermedad y la resolución de los síntomas.

The case report of a 37-year-old patient with history of having received radiotherapy due to a tumor lesion in the right frontal region is presented, who attended to the Institute of Neurology and Neurosurgery in Cuba because of intense headache and left hemiparesis. After carrying out the necessary examinations, the clinical-imaging diagnosis of a radionecrosis lesion in the contralateral hemisphere was established, which was corroborated in the pathological examination once the tumor was removed; then, immunotherapy was indicated. The patient had a favorable clinical course because the control of the disease was achieved as well as the resolution of symptoms.

Exploration of potential active ingredients and mechanism of action of Xihuang pill-medicated serum against glioma based on HPLC-Q-TOF-MS/MS, network pharmacology and experimental verification / 药学学报

Qualitative analysis of the ingredients absorbed into blood and their metabolites of Xihuang pill (XHP) were conducted using high-performance liquid chromatography quadrupole time-of-flight mass spectrometry (HPLC-Q-TOF-MS/MS) technology. Network pharmacology was used to explore the potential anticancer mechanisms of the ingredients against glioma, and their specific mechanisms were validated through molecular docking and experimental verification. SD rats were intragastrically administered with XHP, and rat serum samples were collected. Ingredients absorbed into blood and their metabolites were identified based on the retention time of chromatographic peaks, accurate molecular mass, characteristic fragment ions, and comparisons with reference substances and literature data. PharmMapper and SwissTarget Prediction databases were used to obtain the targets of the XHP-medicated serum, while GeneCards, OMIM, PharmGKB, TTD, and DrugBank databases were used to obtain glioma disease targets. The "component-target" network relationship diagram was constructed using Cytoscape 3.9.1 software. The protein-protein interaction (PPI) network diagram was constructed using the STRING database, and the targets were analyzed using GO and KEGG analyses. Molecular docking was used to verify the binding ability of core targets with their corresponding compounds in XHP-medicated serum. The potential mechanism of the anti-glioma effect of 11-keto-β-boswellic acid (KBA), a representative component of XHP-medicated serum, was verified using CCK-8 and Western blot assays. A total of 40 compounds were identified in the XHP-medicated serum, including 28 prototype components and 12 metabolites. The network pharmacology results showed that elemonic acid, 3-acetyl-β-boswellic acid, KBA, α-boswellic acid, and other 5 compounds might be the active ingredients of XHP-medicated serum in the treatment of glioma. Glutathione reductase (GSR), glucose-6-phosphate dehydrogenase (G6PD), ATP-citrate lyase (ACLY), aldo-keto reductase family 1 member B1 (AKR1B1) and glutaredoxin (GLRX) were identified as key targets, involving pathways such as glutathione metabolism and the pentose phosphate pathway. Further cell experiments showed that KBA significantly inhibited the proliferation of T98G cells with an IC50 of 30.96 μmol·L-1, and KBA (30 μmol·L-1) significantly downregulated the protein expression levels of GSR in T98G cells. In summary, XHP-medicated serum may exert its anti-glioma effect by regulating GSR and G6PD-targeted pathways involved in glutathione metabolism. These results provide valuable evidence for further investigating the mechanism of XHP in treating glioma. The animal welfare and experimental procedures were approved by the Ethical Committee of Laboratory Animals at Nanjing University of Chinese Medicine (approval No. ACU221001).

Factors Associated with Site-specific Distribution of Glioblastoma / 肿瘤防治研究

The treatment of glioblastoma, the most prevalent malignant tumor in the central nervous system, poses considerable challenges. Glioblastoma multiforme, classified as a grade Ⅳ highly malignant brain glioma by the World Health Organization, is typically managed through a combination of surgery, postoperative chemotherapy, and radiotherapy. The treatment of glioblastoma is complicated by its infiltrative nature, genetic heterogeneity, and presence of the blood-brain barrier. Almost all cases of glioblastoma experience recurrence despite aggressive therapy, exploring the development of updated molecular treatment strategies that can improve overall efficacy. A crucial aspect in modern neurosurgery is the precise delineation of brain regions in terms of their anatomy and function. It serves as the fundamental basis for investigating variations in the distribution of brain gliomas. Hence, this review will elucidate the origin of glioblastomas and analyze the potential factors contributing to the spatially specific distribution of gliomas on the basis of a theoretical framework of brain connectomics research. Molecular characteristics, information pathways, tumor microenvironment landscape, and immunology will inform the analysis. We aim to identify novel biomolecular targets and therapeutic pathways to gain scientific insights for effective glioblastoma treatment.

Effect of Diffuse Glioma with Precentral Gyrus Invasion on Interhemispheric Brain Activation： A Task-based FMRI Study / 中山大学学报(医学科学版)

ObjectivesTo explore the effect of diffuse glioma with precentral-gyrus invasion on fMRI activation maps by grasping T-fMRI. MethodsA total of 56 diffuse glioma patients were divided into precentral-gyrus invasion （PGI： n=21） and precentral-gyrus non-invasion （PGNI： n=35） groups. Three statistical thresholds （P value： 10-4， P1； 10-6， P2； 10-8， P3） were set to obtain the activation maps accordingly （V1， V2 and V3）. The interhemispheric and bilateral precentral gyrus activation volumes ratios （IAVR and PAVR） were calculated， respectively. The activation volumes ［△V1=V1-V2； △V2=V2-V3； △Vn （ipsilateral）/△Vn’ （contralateral）， n=1， 2］ within two statistical thresholds and the corresponding interhemispheric ratio was further compared. In addition， the associations of tumor characteristics with IAVR and PAVR were analyzed. ResultsCompared with PGNI， PGI showed significantly decreased IAVR at p1， and the same trends of PAVR in PGI at P1 and P2 （P＜0.05）. However， neither IAVR nor PAVR showed significant differences at P3. PGI showed significantly lower ratios of △V1/△V1’ than PGNI （P=0.02）， except for △V2/△V2’. Additionally， within PGI， PAVR was negatively correlated with tumor volume （P=0.043）， and the distance from the tumor to the hand-knob was positively correlated with the IAVR and PAVR （P＜0.05）. ConclusionDiffuse glioma invading eloquent areas tended to affect interhemispheric asymmetry of activation at relatively lower statistical thresholds than diffuse glioma without invasion， rather than stricter statistical thresholds. Multiple ranges of statistical thresholds were recommended to analyze T-fMRI.

New Advances in the Use of 18F-FET PET in the Diagnosis and Management of Adult High-Grade Gliomas / 罕见病研究

Gliomas are the most common primary intracranial tumors in adults, among which high-grade glioma patients are characterized by short survival and poor prognosis. The diagnosis, treatment, evaluation of effective treatments, and prognosis prediction of high-grade gliomas are of great significance for improving patient survival. Conventional enhanced magnetic resonance imaging has deficiencies in delineating tumor extent, identifying tumor progression and treatment-related changes. Therefore, there is a broad consensus to incorporate amino acid PET, and 18F-FET PET inparticular, into the diagnostic and therapeutic process of high-grade gliomas. In this article, we review the new research progress of 18F-FET PET in the diagnosis and treatment of adult high-grade glioma in recent years.

Effects of anlotinib on the malignant phenotype of glioma cells by mediating NF-κB signaling pathway / 中国药房

OBJECTIVE To investigate the effects of anlotinib on the malignant phenotype of glioma cells by regulating the nuclear factor-κB （NF-κB） signaling pathway. METHODS Human glioma T98G cells were cultured in vitro， and 5-fluorouracil was used as positive control to investigate the effects of different concentrations of anlotinib （5， 10， 20 μmol/L） on the ability of proliferation， adhesion， migration and invasion， the expressions of epithelial-mesenchymal transition （EMT） related proteins [E-cadherin， N-cadherin， vimentin and fibronectin （FN）]. NF- κB signaling pathway inhibitor （BAY 11-7082） and activator （prostratin） were additionally used to verify the possible mechanism of the above effects of anlotinib. RESULTS Anlotinib with 5， 10， 20 μmol/L could significantly decrease the activity of cell proliferation （except for 5 μmol/L anlotinib group）， migration rate， and the number of adherent cells and invasive cells， could significantly up-regulate the expression of E-cadherin protein while down-regulate the expressions of N-cadherin， vimentin and FN protein （P＜0.05）； the effect of 20 μmol/L anlotinib was similar to that of positive control （P＞0.05）. Compared with 10 μmol/L anlotinib， pathway inhibitor could significantly decrease the ability of proliferation， adhesion， migration and invasion， and the expressions of N-cadherin， vimentin， FN and phosphorylated NF-κB p65 protein， while could significantly up-regulate the expression of E-cadherin protein （P＜0.05）； above indexes were reversed significantly by pathway activator （P＜0.05）. CONCLUSIONS Anlotinib may inhibit the proliferation， adhesion， migration and invasion of human glioma T98G cells， which may be associated with the inhibition of the NF-κB signaling pathway， thus inhibiting cell EMT-like processes.

Expression of brain-derived neurotrophic factor and formation of migrasome increases in the glioma cells induced by the adipokinetic hormone

SUMMARY OBJECTIVE: It has been previously shown that brain-derived neurotrophic factor is linked with various types of cancer. Brain-derived neurotrophic factor is found to be highly expressed in multiple human cancers and associated with tumor growth, invasion, and metastasis. Adipokinetic hormones are functionally related to the vertebrate glucagon, as they have similar functionalities that manage the nutrient-dependent secretion of these two hormones. Migrasomes are new organelles that contain numerous small vesicles, which aid in transmitting signals between the migrating cells. Therefore, the aim of this study was to investigate the effects of Anax imperator adipokinetic hormone on brain-derived neurotrophic factor expression and ultrastructure of cells in the C6 glioma cell line. METHODS: The rat C6 glioma cells were treated with concentrations of 5 and 10 Anax imperator adipokinetic hormone for 24 h. The effects of the Anax imperator adipokinetic hormone on the migrasome formation and brain-derived neurotrophic factor expression were analyzed using immunocytochemistry and transmission electron microscope. RESULTS: The rat C6 glioma cells of the 5 and 10 μM Anax imperator adipokinetic hormone groups showed significantly high expressions of brain-derived neurotrophic factor and migrasomes numbers, compared with the control group. CONCLUSION: A positive correlation was found between the brain-derived neurotrophic factor expression level and the formation of migrasome, which indicates that the increased expression of brain-derived neurotrophic factor and the number of migrasomes may be involved to metastasis of the rat C6 glioma cell line induced by the Anax imperator adipokinetic hormone. Therefore, the expression of brain-derived neurotrophic factor and migrasome formation may be promising targets for preventing tumor proliferation, invasion, and metastasis in glioma.

Larotrectinib versus infigratinib for adult patients with both glioma and tyrosine kinase alterations after failure of initial therapies: Efficacy and safety analysis

Abstract Objectives To compare the efficacy and safety of larotrectinib with those of infigratinib in adult glioma patients with tyrosine kinase alterations. Methods Patients received oral infigratinib 125 mg (IN cohort, n = 125) or oral larotrectinib (LB cohort, n = 105) until unacceptable toxicity or disease progression. Results Duration of treatment was longer in the LB cohort than in the IN cohort (8 [9.5-6.25] months vs. 5.5 [6-5.25] months, p < 0.0001). Patients with partial responses (p = 0.0424) and overall survival (p = 0.03) were higher in the IN cohort than those in the LB cohort. The number of patients with disease progression was higher in the LB cohort (p = 0.0015). All the patients reported diarrhea, fatigue, vomiting, constipation, and decreased appetite. Patients in the IN cohort reported hyperphosphatemia, hyperlipasemia, stomatitis, dry skin, alopecia, dyspepsia, onycholysis, palmar-plantar erythrodysesthesia, nail disorders, and dry eyes. Patients in the LB cohort reported upper respiratory tract infections, pyrexia, cough, anemia, bacterial/viral infections, conjunctivitis, urinary tract infections, headaches, ataxia, dizziness, and muscle tremors. A total of 30 (24 %) and 40 (38 %) patients from the IN and the LB cohorts died at the follow-up of 18 months (p = 0.03). Patients who received bevacizumab initial therapy had higher overall survival (p = 0.048). Conclusions Infigratinib has higher efficacy and overall survival than larotrectinib but has higher adverse effects in the management of both glioma and tyrosine kinase alterations after failure of initial therapies. Initial bevacizumab therapy is associated with a higher overall survival.

Glioma of the optic nerve and chiasm: a case report / Glioma óptico-quiasmático: um relato de caso

ABSTRACT This article reports the case of an 11-year-old male patient with a history of proptosis and low progressive visual acuity in the left eye. He presented with a best corrected visual acuity of 20/25 in the right eye and light perception in the left eye. Exotropia and limitation in adduction were observed in the left eye. On automated perimetry, inferiortemporal quadrantopsia was observed in the right eye, while total scotoma was observed in the left eye. On magnetic resonance imaging, there was an expansive lesion in the left optic nerve, extending to the brainstem with chiasmatic involvement. This article aims to report a case of optic pathway glioma, as well as to discuss its clinical findings and their interconnection with the current literature.

RESUMO Este artigo relata o caso de um paciente do sexo masculino, 11 anos de idade, com história de proptose e baixa de acuidade visual progressiva. Ao exame oftalmológico apresentava melhor acuidade visual de 20/25 em olho direito e percepção de luz em olho esquerdo. Existia exotropia e limitação à adução no olho esquerdo. À campimetria automatizada, observou-se quadrantopsia temporal inferior em olho direito e escotoma total em olho esquerdo. À ressonância magnética, evidenciou-se lesão expansiva em trajeto do nervo óptico esquerdo estendendo-se até região do tronco encefálico, com acometimento quiasmático. O objetivo deste artigo é relatar o glioma de vias ópticas, bem como discutir os achados e sua interligação com a literatura atual.

Advances in diffuse glial tumors diagnosis / Avanços no diagnóstico dos gliomas difusos

Abstract In recent decades, there have been significant advances in the diagnosis of diffuse gliomas, driven by the integration of novel technologies. These advancements have deepened our understanding of tumor oncogenesis, enabling a more refined stratification of the biological behavior of these neoplasms. This progress culminated in the fifth edition of the WHO classification of central nervous system (CNS) tumors in 2021. This comprehensive review article aims to elucidate these advances within a multidisciplinary framework, contextualized within the backdrop of the new classification. This article will explore morphologic pathology and molecular/genetics techniques (immunohistochemistry, genetic sequencing, and methylation profiling), which are pivotal in diagnosis, besides the correlation of structural neuroimaging radiophenotypes to pathology and genetics. It briefly reviews the usefulness of tractography and functional neuroimaging in surgical planning. Additionally, the article addresses the value of other functional imaging techniques such as perfusion MRI, spectroscopy, and nuclear medicine in distinguishing tumor progression from treatment-related changes. Furthermore, it discusses the advantages of evolving diagnostic techniques in classifying these tumors, as well as their limitations in terms of availability and utilization. Moreover, the expanding domains of data processing, artificial intelligence, radiomics, and radiogenomics hold great promise and may soon exert a substantial influence on glioma diagnosis. These innovative technologies have the potential to revolutionize our approach to these tumors. Ultimately, this review underscores the fundamental importance of multidisciplinary collaboration in employing recent diagnostic advancements, thereby hoping to translate them into improved quality of life and extended survival for glioma patients.

Resumo Nas últimas décadas, houve avanços significativos no diagnóstico de gliomas difusos, impulsionados pela integração de novas tecnologias. Esses avanços aprofundaram nossa compreensão da oncogênese tumoral, permitindo uma estratificação mais refinada do comportamento biológico dessas neoplasias. Esse progresso culminou na quinta edição da classificação da OMS de tumores do sistema nervoso central (SNC) em 2021. Esta revisão abrangente tem como objetivo elucidar esses avanços de forma multidisciplinar, no contexto da nova classificação. Este artigo irá explorar a patologia morfológica e as técnicas moleculares/genéticas (imuno-histoquímica, sequenciamento genético e perfil de metilação), que são fundamentais no diagnóstico, além da correlação dos radiofenótipos da neuroimagem estrutural com a patologia e a genética. Aborda sucintamente a utilidade da tractografia e da neuroimagem funcional no planejamento cirúrgico. Destacaremos o valor de outras técnicas de imagem funcional, como ressonância magnética de perfusão, espectroscopia e medicina nuclear, na distinção entre a progressão do tumor e as alterações relacionadas ao tratamento. Discutiremos as vantagens das diferentes técnicas de diagnóstico na classificação desses tumores, bem como suas limitações em termos de disponibilidade e utilização. Além disso, os crescentes avanços no processamento de dados, inteligência artificial, radiômica e radiogenômica têm grande potencial e podem em breve exercer uma influência substancial no diagnóstico de gliomas. Essas tecnologias inovadoras têm o potencial de revolucionar nossa abordagem a esses tumores. Em última análise, esta revisão destaca a importância fundamental da colaboração multidisciplinar na utilização dos recentes avanços diagnósticos, com a esperança de traduzi-los em uma melhor qualidade de vida e uma maior sobrevida.

Biomarcadores genéticos en sangre, una nueva herramienta para el diagnóstico, pronóstico y supervivencia en pacientes con gliomas de alto grado / Genetic biomarkers in blood, a new tool for diagnosis, prognosis, and survival in patients with high-grade gliomas / Biomarcadores genéticos no sangue, uma nova ferramenta para diagnóstico, prognóstico e sobrevida em pacientes com gliomas de alto grau

Durante mucho tiempo, la clasificación de los tumores del sistema nervioso central (SNC) se ha basado en hallazgos histológicos respaldados por pruebas complementarias, como la inmunohistoquímica, establecidas en tejidos. La quinta edición de la clasificación de tumores del SNC de la Organización Mundial de la Salud (OMS), publicada en 2021 (SNC-5) incorpora numerosos marcadores moleculares con utilidad clínico-patológica que son importantes para una clasificación más precisa de las neoplasias del SNC. Ello permiten ayudar a definir los gliomas difusos del adulto, oligodendroglioma mutado para el gen de la IDH (isocitrato deshidrogenasa láctica), con codeleción 1p/19q grados 2 a 3, astrocitoma mutado para IDH sin codeleción 1p/19q, grados 2 a 4 y glioblastoma (GBM) silvestre para IDH. La mediana de sobrevida en los pacientes con GBM es de solo 14.6 meses, debido a la resistencia al protocolo de terapia más utilizado en el mundo, el cual involucra cirugía, radioterapia y quimioterapia con temozolamida (TMZ), un potente alquilante genotóxico. Los criterios de selección del tratamiento y la estimación del pronóstico en pacientes con esta enfermedad son clínico-patológicos. En los últimos años se reportaron numerosas alteraciones moleculares que amplían la comprensión de la biología de estos tumores, pero solo unas pocas influyen como biomarcadores en la toma de decisiones clínicas y del tratamiento. En este artículo se revisan las alteraciones moleculares reportadas para gliomas de alto grado en sangre periférica, también se resalta la importancia de estandarizar nuevos biomarcadores junto a los hallazgos histológicos para mejorar el conocimiento de estos tumores.

For a long time, the classification of central nervous system (CNS) tumors has been based on histological findings supported by complementary tests, such as immunohistochemistry, established in tissues. The fifth edition of the World Health Organization (WHO) Classification of Tumors of the Central Nervous System, published in 2021 (CNS-5), incorporates numerous molecular markers with clinical-pathological utility that are important for a more accurate classification of CNS neoplasms. These markers help to define adult diffuse gliomas, including IDH-mutant oligodendroglioma with 1p/19q codeletion (grades 2-3), IDH-mutant astrocytoma without 1p/19q codeletion (grades 2-4), and wild-type IDH glioblastoma (GBM). The median survival in patients with GBM is only 14.6 months, primarily due to resistance to the most widely used treatment protocol worldwide, which involves surgery, radiotherapy, and chemotherapy with temozolomide (TMZ), a potent genotoxic alkylating agent. The selection criteria for treatment and the estimation of prognosis in patients with this disease are predominantly based on clinical and pathological factors. In recent years, numerous molecular alterations have been reported, expanding our understanding on the biology of these tumors. However, only a few of these molecular alterations serve as biomarkers that influence clinical decision-making and treatment strategies. This article reviews the molecular alterations reported in peripheral blood for high-grade gliomas and emphasizes the importance of standardizing new biomarkers alongside histological findings to enhance our knowledge of these tumors.

Por muito tempo, a classificação dos tumores do sistema nervoso central (SNC) baseou-se em achados histológicos respaldados por exames complementares, como a imuno-histoquímica, estabelecidos nos tecidos. A quinta edição da classificação de tumores do SNC da Organização Mundial da Saúde (OMS), publicada em 2021 (CNS-5), incorpora inúmeros marcadores moleculares com utilidade clinicopatológica importantes para uma classificação mais precisa das neoplasias do SNC. Isso permite definir gliomas difusos adultos, oligodendroglioma mutado para o gene IDH (lactic isocitrato desidrogenase), com codeleção 1p/19q graus 2 a 3, astrocitoma mutado para IDH sem codeleção 1p/19q, graus 2 a 4 e wild- tipo glioblastoma (GBM) para IDH. A sobrevida mediana em pacientes com GBM é de apenas 14,6 meses, devido à resistência ao protocolo terapêutico mais utilizado no mundo, que envolve cirurgia, radioterapia e quimioterapia com temozolamida (TMZ), um potente alquilador genotóxico . Os critérios de seleção para o tratamento e estimativa do prognóstico em pacientes com essa doença são clínico-patológicos. Nos últimos anos, foram relatadas inúmeras alterações moleculares que ampliam o entendimento da biologia desses tumores, mas apenas algumas influenciam na decisão clínica e terapêutica como biomarcadores. Este artigo revisa as alterações moleculares relatadas para gliomas de alto grau no sangue periférico, destacando também a importância da padronização de novos biomarcadores juntamente com os achados histológicos para melhorar o conhecimento desses tumores

Role of cyclin D1 in glial tumors—A retrospective and observational study

Aim: High-grade glial tumors remain as one of the most lethal malignancies. Cyclin D1 is expressed in some human malignancies and is the potential target of intervention. The present study aims to determine the relationship of cyclin D1 expression with other clinicopathological parameters. Materials and Methods: A cross-sectional study was carried out in a tertiary care center. Biopsy proven 66 cases of glial tumor patients were included in the study. The patients with incomplete clinical details were excluded from the study. Immunohistochemistry using antibodies for IDH 1 and cyclin d1 was done in all the cases. Glial tumors were reclassified according to WHO 2016 classification. Data analysis was performed using SPSS 26.0 for the windows. Result: Among 66 patients, 49 (74.3%) were males and 17 (25.7%) were females. The age of the patients ranged from 20 years to 70 years. Overall, 6.02% were of grade I Glial tumors, 22.7% were of grade II Glial tumors, 19.6% patients were of grade III Glial tumors, and 51.6% patients were of grade IV Glial tumors. Of 66 samples tested cyclin D1 was positive in 25 (37.87%) as high expressers and 7 (10.60%) were low expressers. Our study showed a significant correlation between the expression of cyclin D1 with grade and IDH mutation status, No significant correlation of cyclin D1 was noted with age or sex of the patient. Conclusion: Cyclin D1 was associated with a higher grade of the glial tumor. It can be a potential marker both for prognosis and treatment of glial tumors.

The 2021 World Health Organization classification of gliomas: an imaging approach / Nova classificação das neoplasias gliais segundo a Organização Mundial da Saúde 2021, com enfoque radiológico

Abstract The purpose of this pictorial essay is to describe the recommendations of the 2021 World Health Organization classification for adult-type and pediatric-type gliomas and to discuss the main modifications in relation to the previous (2016) classification, exemplified by imaging, histological, and molecular findings in nine patients followed at our institutions. In recent years, molecular biomarkers have gained importance in the diagnosis and classification of gliomas, mainly because they have been shown to correlate with the biological behavior and prognosis of such tumors. It is important for neuroradiologists to familiarize themselves with this new classification of central nervous system tumors, so that they can use this knowledge in evaluating and reporting the imaging examinations of patients with glioma.

Resumo O propósito deste ensaio iconográfico é descrever e discutir as novas recomendações da Organização Mundial da Saúde de 2021, referente aos gliomas dos tipos adulto e infantil, e suas principais diferenças com a classificação anterior (2016), exemplificadas com imagens de nove casos de pacientes atendidos nas nossas instituições. Recentemente, há uma crescente significância dos marcadores moleculares no diagnóstico e classificação dos gliomas e tumores do sistema nervoso central, principalmente pela correlação com o comportamento biológico e o prognóstico. É importante que os neurorradiologistas estejam familiarizados com a nova classificação dos tumores do sistema nervoso central para a prática clínica, na avaliação e emissão de laudos e opiniões nas imagens dos pacientes com gliomas.

Ventajas de la secuenciación de próxima generación sobre la hibridación fluorescente in situ para detectar la codeleción 1p/19q en oligodendrogliomas / Advantages of next generation sequencing over fluorescent in situ hybridization to detect 1p/19q codeletion in oligodendroglioma / Vantagens do sequenciamento de próxima geração sobre a hibridização fluorescente in situ para detectar codeleção 1p/19q em oligodendrogliomas

El perfil molecular de los gliomas permite garantizar la precisión del diagnóstico, informar el pronóstico e identificar opciones de tratamiento. Esta revisión tiene como objetivo exponer que con la secuenciación de próxima generación (NSG) el diagnóstico de los pacientes con oligodendrogliomas puede ser más exacto. Además, con un dispositivo de diagnóstico in vitro, basado en la NSG (F1CDx), en el que se utilizan los bloques de parafina de gliomas para analizar hasta 395 genes relacionados con cáncer (incluido IDH 1 y 2), se puede también informar la pérdida de la totalidad del brazo corto del cromosoma 1 y del brazo largo del cromosoma 19 (codeleción 1p/19q), a diferencia de la hibridación fluorescente in situ (FISH) que detecta desde la más mínima deleción, lo cual los hace sensibles pero no específicos ya que el FISH es incapaz de distinguir entre la pérdida de la totalidad del brazo del cromosoma y una deleción focal. Esta distinción es importante ya que la sobrevida es inferior en tumores con deleción parcial en rela­ción con los oligodendrogliomas, que tienen por definición la pérdida total de ambos cromosomas. Se hace también alusión a otras plataformas genómicas como GlioSeq y GLIO-DNA panel, que pueden cumplir la misma función. En conclusión, la F1CDx puede determinar con precisión 1p/19q con una concordancia del 96.7% frente a FISH. Los casos en que el FISH dio positivo y no concordaban con F1CDx, era porque no se trataba de oligodendrogliomas. F1CDx también analiza todos los genes que permiten la aproximación más exacta al diagnóstico de oligodendroglioma.

Molecular profiling of gliomas helps ensure diagnostic accuracy, inform prognosis, and identify treatment options. This review aims to show that with next generation sequencing (NGS) the diagnosis of patients with oligodendrogliomas can be more accurate. In addition, with an in vitro diagnostic device, based on NSG (F1CDx), in which glioma paraffin blocks are used to analyze up to 395 cancer-related genes (including IDH 1 and 2), it is also possible to report the loss of the entire short arm of chromosome 1 and the long arm of chromosome 19 (1p/19q codeletion), unlike fluorescence in situ hybridization (FISH) that detects even the slightest deletion, making them sensitive but not specific, as FISH is unable to distinguish between the loss of the entire arm of the chromosome and a focal deletion. This distinction is important since survival is lower in tumors with partial deletion compared to oligodendrogliomas, which by definition have the total loss of both chromosomes. Reference is also made to other genomic platforms such as GlioSeq and GLIO-DNA panel, which can fulfill the same function. In conclusion, the F1CDx can accurately determine 1p/19q with a concordance of 96.7% against FISH. The cases in which the FISH was positive and did not agree with F1CDx, it was because they were not oligodendrogliomas. F1CDx also analyzes all the genes that allow the most accurate approach to the diagnosis of oligodendroglioma.

O perfil molecular de gliomas ajuda a garantir a precisão do diagnóstico, informar o prognóstico e identificar as opções de tratamento. Esta revisão tem como objetivo mostrar que com o sequenciamento de próxima geração (NSG) o diagnóstico de pacientes com oligodendrogliomas pode ser mais preciso. Além disso, com um dispositivo de diagnóstico in vitro baseado em NSG (F1CDx), no qual blocos de parafina de glioma são usados para analisar até 395 genes relacionados ao câncer (incluindo IDH 1 e 2), também é possível relatar a perda do todo o braço curto do cromossomo 1 e o braço longo do cromossomo 19 (codeleção 1p/19q), ao contrário da hibridização fluorescente in situ(FISH) que detecta desde a menor deleção, o que os torna sensíveis, mas não específicos, pois o FISH é incapaz de distinguir entre a perda de todo o braço do cromossomo e uma deleção focal. Essa distinção é importante, pois a sobrevida é menor nos tumores com deleção parcial em relação aos oligodendrogliomas, que por definição apresentam a perda total de ambos os cromossomos. Também é feita referência a outras plataformas genômicas, como GlioSeq e painel GLIO-DNA, que podem cumprir a mesma função. Em conclusão, o F1CDx pode determinar com precisão 1p/19q com uma concordância de 96,7% versus FISH. Os casos em que FISH foi positivo e não concordaram com F1CDx, foi porque não eram oligodendrogliomas. O F1CDx também analisa todos os genes que permitem a abordagem mais precisa para o diagnóstico de oligodendroglioma.

Anti-glioma mechanism of pterostilbene by regulating apoptosis and GSDME-mediated pyroptosis pathways: a study based on network pharmacology and experimental research / 中国中药杂志

This study aimed to explore the anti-glioma effect of natural compound pterostilbene(PTE) through regulating pyroptosis and apoptosis pathways, and to analyze the possible anti-glioma pathways and targets of PTE by network pharmacology and molecular docking. In this study, the action targets of PTE and the glioma targets were obtained by network pharmacology to construct a target network and a protein-protein interaction(PPI) network to predict the possible action targets of PTE against glioma. Molecular docking was performed on the core targets by AutoDock and the action pathways of PTE against glioma were predicted by enrichment analysis. In addition, the effect of PTE on the viability of U87MG and GL261 glioma cells was detected by CCK-8 assay. Clone formation assay and cell scratching assay were used to explore the effect of different concentrations of PTE on the proliferation and migration, respectively of glioma cells. Hoechst staining was used to observe PTE-induced apoptosis in glioma cells. The changes in mitochondrial membrane potential were detected by JC-1 staining. The pyroptosis-inducing effect of PTE on glioma cells was observed by inverted microscopy and lactate dehydrogenase(LDH) assay. Hoechst 33342/PI dual staining assay was performed to detect the integrity of glioma cell membranes. The expressions of pyroptosis and apoptosis-related proteins in glioma cells after PTE induction were determined by Western blot. In this study, 37 anti-glioma targets of PTE were obtained, and enrichment analysis suggested that PTE exerted anti-glioma effects through various signaling pathways including cancer pathway, proteoglycan in cancer, PI3K/AKT pathway, and apoptosis regulatory pathway. Molecular docking revealed that PTE had good binding activity with the main targets. Compared with the control group, PTE significantly reduced the viability as well as the proliferation, migration and adhesion abilities of U87MG and GL261 cells; it induced the apoptosis of the two glioma cells and the decrease of mitochondrial membrane potential in U87MG cells, and the effects increased with the increase of drug concentration. Compared with the conditions in the control group, glioma cells in the PTE group had increased pyroptosis-specific appearance and gradually increased LDH release; the number of PI positive cells was significantly elevated with the increase of PTE concentration as revealed by Hoechst 33342/PI staining; the expression levels of apoptosis-related factors cleaved PARP1 and B-cell lymphoma-2(Bcl-2) associated X(BAX) in the PTE group were markedly up-regulated, while the expression level of Bcl-2 was markedly down-regulated; the activation levels of pyroptosis-related proteins cleaved caspase-3 and gasdermin E-N(GSDME-N) had a remarkable rise in the PTE group, while no significant changes were found in the activation levels of gasdermin D-N(GSDMD-N) and cleaved caspase-1. In summary, PTE plays an anti-glioma role by inhibiting cell viability, proliferation, and migration and activating the caspase-3/GSDME-mediated pyroptosis pathway and mitochondrial apoptosis pathway.

Study on inhibitory effects and mechanism of silymarin on glioma in vivo and in vitro / 中国药房

OBJECTIVE To investigate the inhibitory effects of silymarin （SM） on glioma in vivo and in vitro and its potential mechanism. METHODS Human glioma cell line U87 cells were randomly divided into control group， SM low- concentration， SM medium-concentration and SM high-concentration groups （50， 100， 200 μg/mL）， protein kinase B （Akt） activator group （SC79 20 μmol/L）， high-concentration of SM combined with Akt activator group （SM 200 μg/mL+SC79 20 μmol/L）. After drug treatment （except for the control group）， optical density （OD） value， clone formation rate， apoptotic rate， the expressions of proliferation/apoptosis-related proteins [proliferating cell nuclear antigen （PCNA）， B-cell lymphoma-2 （Bcl-2）， Bcl- 2-associated X protein （Bax）， caspase-3]， the phosphorylation levels of Akt/mitogen-activated protein kinase （MAPK） signaling pathway related proteins [Akt， p38 MAPK， extracellular signal-regulated kinase 1/2 （ERK1/2）] were detected in each group. The xenograft tumor model in nude mice was established by injecting U87 cells subcutaneously via the right armpit， and then divided into control group， SM low-dose， SM medium-dose and SM high-dose groups （25， 50， 100 mg/kg）， Akt activator group （SC79 40 mg/kg）， high-dose of SM combined with Akt activator group （SM 100 mg/kg+SC79 40 mg/kg）， with 5 mice in each group. After drug intervention （except for the control group of nude mice）， the tumor mass was weighed and the tumor volume was calculated. RESULTS Compared with control group， the OD values， clone formation rates， protein expressions of PCNA and Bcl- 2， phosphorylation levels of Akt， p38 MAPK and ERK1/2 in SM groups， tumor mass and volume in nude mice of SM groups were all decreased significantly， while the apoptosis rates， protein expressions of Bax and caspase-3 were increased significantly， in a dose-dependent manner （P＜0.05）；the trend of changes in the above indicators in the Akt activator group was opposite （P＜ 0.05）， and Akt activator could significantly attenuate the inhibitory effect of high-concentration/high-dose SM on glioma in vivo and in vitro （P＜0.05）. CONCLUSIONS SM may promote the apoptosis of U87 cells， and inhibit its proliferation， clone formation and tumor growth in xenograft nude mice by inhibiting Akt/MAPK signaling pathway.

Piroctone olamine disrupts mitochondrial dynamics in glioma cells through the PI3K/AKT pathway / 南方医科大学学报

OBJECTIVE@#To investigate the growth-inhibitory and pro-apoptotic effects of piroctone olamine (PO) on glioma cells and explore the underlying mechanism.@*METHODS@#Human glioma cell lines U251 and U373 were treated with PO and the changes in cell proliferation were detected using CCK-8 assay and EdU assay. Clone formation assay and flow cytometry were used to examine the changes in clone formation ability and apoptosis of the treated cells. Mitochondrial membrane potential of the cells and morphological changes of the mitochondria were detected using JC-1 staining and a fluorescence probe, respectively. The expressions of mitochondrial fission protein DRP1 and the fusion protein OPA1 were determined with Western blotting. Transcriptome sequencing and differential gene enrichment analysis was performed, and the expression levels of PI3K, AKT and p-AKT in the treated cells were verified using Western blotting.@*RESULTS@#CCK-8 assay showed that PO significantly inhibited the proliferation of U251 and U373 cells in a time- and dose-dependent manner (P < 0.001). EdU test showed that the proliferative activity of PO-treated cells was significantly decreased, and the number of cell colonies also decreased significantly (P < 0.01). PO treatment significantly increased apoptotic rates (P < 0.01), decreased mitochondrial membrane potential and caused obvious changes in mitochondrial morphology of the cells. Pathway enrichment analysis showed that the down-regulated genes were significantly enriched in the PI3K/AKT pathway, which was verified by Western blotting showing significantly down-regulated expression levels of PI3K, AKT and p-AKT in PO-treated cells (P < 0.05).@*CONCLUSION@#PO interferes with mitochondrial fusion and fission function through the PI3K/AKT pathway, thereby inhibiting the proliferation and increasing apoptosis of glioma cells.

Correlation Between Apparent Diffusion Coefficient and IDH-1/1p19q Genotype of Glioma / 肿瘤防治研究

Objective To investigate the correlation between ADC value and glioma IDH-1/1p19q genotype. Methods The MRI features and molecular pathological results of 69 patients with pathologically confirmed diagnosis of WHO grade Ⅱ/Ⅲ glioma between March 2013 and December 2020 were retrospectively analyzed. The diagnostic performance of ADC values on glioma genotypes (IDH-1, 1p19q) was evaluated using the ROC curve of the subjects' working characteristics. Results The ADCmean, ADCmin, rADCmean, and rADCmin in the IDH-1 mutation group were significantly higher than those in the IDH-1 wild group (P < 0.05, P < 0.01, P < 0.05, P < 0.01). The use of the rADCmin threshold (0.979×103mm2/s) had the highest efficacy (AUC=0.770) for diagnosis of IDH-1 mutant and IDH-1 wild-type gliomas as well as sensitivity and specificity of 84.61% and 59.09%, respectively. Conclusion ADC can be used as an imaging biomarker for noninvasive prediction of IDH-1 mutant and wild-type Ⅱ /Ⅲ gliomas.

Temporal and spatial stability of the EM/PM molecular subtypes in adult diffuse glioma / 医学前沿

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.

Effects of C10orf10 on growth and prognosis of glioma under hypoxia / 中南大学学报(医学版)

OBJECTIVES@#Glioma is the most common malignant tumor in the central nervous system, and the hypoxic microenvironment is prevalent in solid tumors. This study aims to investigate the up-regulation of genes under the condition of hypoxia and their roles in glioma growth, as well as their impact on glioma prognosis.@*METHODS@#The hypoxia-related dataset with glioma was screened in the Gene Expression Omnibus database (GEO), and the differentially expressed genes were analyzed between hypoxia and normoxia through bioinformatics, and chromosome 10 open reading frame 10 (C10orf10) was verified and screened in hypoxia-treated cells through real-time PCR and Western blotting. The Cancer Genome Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA) datasets were downloaded to analyze the mRNA expression of C10orf10 in different grades of glioma and its impact on prognosis. The glioma specimens and follow-up data of 68 gliomas who underwent surgical treatment in Xiangya Hospital of Central South University from March 2017 to January 2021 were collected, and real-time PCR was used to detect the mRNA expression of C10orf10 in different grades of glioma, and the Kaplan-Meier method was used to analyze the relationship between the expression C10orf10 and prognosis. The glioma cells, which could interfere the expression of C10orf10, were constructed, and the effect of C10orf10 on the proliferation of glioma cells was evaluated by cell counting kit-8 (CCK-8) and colony formation assays.@*RESULTS@#Compared with the condition of normoxia, the expression levels of C10orf10 mRNA and protein were significantly up-regulated in glioma cells under hypoxia (P<0.001), and the mRNA expression level of C10orf10 in glioma tissues was up-regulated with the increase of WHO grade in glioma (P<0.001). Based on Kaplan-Meier survival analysis, the higher the mRNA expression level of C10orf10 was, the shorter the survival time of the patient was (P<0.05). And the expression of C10orf10 mRNA was higher in recurrent gliomas than that in primary gliomas in the CGGA database (P<0.001). Knockdown of C10orf10 could significantly inhibit the growth of glioma cells both under hypoxia and normoxia (both P<0.001).@*CONCLUSIONS@#The expression level of C10orf10 can promote the proliferation and prognosis of glioma, which is expected to become a prognostic marker and therapeutic target for glioma.