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1.
Acta Medica Philippina ; : 82-86, 2024.
Artículo en Inglés | WPRIM | ID: wpr-1012457

RESUMEN

@#Although melanoma only accounts for 1% of skin cancers, it is responsible for most skin cancer deaths. Glioblastoma multiforme, a high-grade astrocytoma, is the most aggressive and devastating primary brain tumor. These two diseases remain to be the biggest therapeutic challenge in both specialties of dermatology and neuro-oncology. A 53-year-old Filipino male who presented with a 2-year history of generalized dark brown and black patches on the body developed weakness and numbness of the left extremities. Biopsy and immunohistochemical staining of the skin revealed nodular melanoma with adjacent regressing melanoma. Biopsy of the intracranial mass showed glioblastoma multiforme. One month after the partial excision of the intracranial mass, the patient expired due to brain herniation. Nodular melanoma and glioblastoma multiforme may occur concomitantly in a patient. A review of the literature suggests a shared genetic predisposition. Its existence carries a poor prognosis and requires early detection to start aggressive treatment.


Asunto(s)
Melanoma , Glioma , Glioblastoma , Asociación
2.
Braz. J. Pharm. Sci. (Online) ; 60: e23380, 2024. graf
Artículo en Inglés | LILACS | ID: biblio-1533983

RESUMEN

Abstract Glioblastoma multiforme is a tumor of the central nervous system. Focal Adhesion Kinase (FAK) and αB-crystalline are two proteins involved in glioblastoma development. In this study, we investigated whether the FAK/αB-crystalline interaction is important for glioblastoma cells, we aimed to investigate the interaction of these two proteins in the glioblastoma multiforme cell line U87-MG. Two peptides named FP01 peptide (derived from αB-crystalline) and FP02 peptide (derived from FAK) were synthesized for this study. Treatment of U87-MG with the peptides FP01 and FP02 in the concentration at 50 µM reduced the viability cellular to around 41% and 51%, respectively. Morphological alterations in the cells treated with the peptides when compared to the control were observed. This study suggests that the interaction between FAK and αB-crystalline is important for the viability of glioblastoma cells


Asunto(s)
Péptidos/efectos adversos , Células/clasificación , Glioblastoma/patología , Proteína-Tirosina Quinasas de Adhesión Focal/efectos adversos , Neoplasias/patología , Línea Celular/clasificación , Sistema Nervioso Central/anomalías
3.
Chinese Journal of Biotechnology ; (12): 3787-3799, 2023.
Artículo en Chino | WPRIM | ID: wpr-1007993

RESUMEN

The aim of this study was to investigate the functional characteristics and in vitro specific killing effect of EGFRvIII CAR-T cells co-expressing interleukin-15 and chemokine CCL19, in order to optimize the multiple functions of CAR-T cells and improve the therapeutic effect of CAR-T cells targeting EGFRvIII on glioblastoma (GBM). The recombinant lentivirus plasmid was obtained by genetic engineering, transfected into 293T cells to obtain lentivirus and infected T cells to obtain the fourth generation CAR-T cells targeting EGFRvIII (EGFRvIII-IL-15-CCL19 CAR-T). The expression rate of CAR molecules, proliferation, chemotactic ability, in vitro specific killing ability and anti-apoptotic ability of the fourth and second generation CAR-T cells (EGFRvIII CAR-T) were detected by flow cytometry, cell counter, chemotaxis chamber and apoptosis kit. The results showed that compared with EGFRvIII CAR-T cells, EGFRvIII-IL-15-CCL19 CAR-T cells successfully secreted IL-15 and CCL19, and had stronger proliferation, chemotactic ability and anti-apoptosis ability in vitro (all P < 0.05), while there was no significant difference in killing ability in vitro. Therefore, CAR-T cells targeting EGFRvIII and secreting IL-15 and CCL19 are expected to improve the therapeutic effect of glioblastoma and provide an experimental basis for clinical trials.


Asunto(s)
Humanos , Receptores Quiméricos de Antígenos/metabolismo , Glioblastoma/metabolismo , Interleucina-15/metabolismo , Quimiocina CCL19/metabolismo , Línea Celular Tumoral , Linfocitos T/metabolismo
4.
Journal of the Philippine Medical Association ; : 75-81, 2023.
Artículo en Inglés | WPRIM | ID: wpr-1006367

RESUMEN

@#Constitutionalmismatch repair deficiency(CMMRD) is a hereditary predisposition of malignancy evident in childhood leukemias, lymphomas, and malignant tumors of the brain, GI tract. It is a very rare condition that affects 1 per 1 million patients. Patients with CMMRD syndrome may also manifest with Neurofibromatosis Type 1 (NF1) phenotypic features, and benign masses, particularly in the gastrointestinal tract. This is a case of a 12-year old male who presented with phenotypic features of NF1, developed Acute Lymphoblastic Leukemia at 7 years old and went into remission. He subsequently developed synchronous Glioblastoma and Poorly differentiated Adenocarcinoma of the rectum.This report aims to raise awareness regarding the possibility of a CMMRD syndrome in pediatric patients who present with phenotypic features of NF1, and in those patients who present with two or more malignancies in their lifetime.


Asunto(s)
Glioblastoma , Leucemia-Linfoma Linfoblástico de Células Precursoras
5.
Journal of Zhejiang University. Science. B ; (12): 698-710, 2023.
Artículo en Inglés | WPRIM | ID: wpr-1010564

RESUMEN

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.


Asunto(s)
Animales , Ratones , Humanos , Neoplasias Encefálicas/genética , Línea Celular Tumoral , Proliferación Celular , Resistencia a Antineoplásicos , Retroalimentación , Regulación Neoplásica de la Expresión Génica , Glioblastoma/metabolismo , MicroARNs/metabolismo , Temozolomida/uso terapéutico , Proteína Forkhead Box O1/metabolismo
6.
Rev. baiana enferm ; 37: e51209, 2023. tab, graf
Artículo en Portugués | LILACS, BDENF | ID: biblio-1529647

RESUMEN

Objetivos: identificar as percepções sobre o bem-estar, apoio social, intensidade dos sintomas e o seu impacto nas atividades diárias de pacientes com cânceres cerebrais e correlacionar os achados com os níveis de adesão aos quimioterápicos antineoplásicos orais. Método: estudo correlacional e transversal, realizado num ambulatório hospitalar universitário de São Paulo, Brasil, entre 2019 e 2020. Utilizou-se instrumento para caracterização da amostra e escalas específicas. Resultados: 26 participantes, mediana de 36,5 anos, 61,5% sexo masculino, 53,9% diagnosticados com glioblastoma; 73,1% apresentaram adesão, rede de apoio social e índice alto de bem-estar. O escore médio de intensidade dos sintomas foi de baixo para médio, com pior pontuação para preocupação no pior estado. A maior adesão relacionou-se ao apoio afetivo, apoio informação, interação social e apoio emocional. Conclusão: a maioria declarou níveis positivos de bem-estar, suporte social e poucos sintomas. A percepção de apoio social e bem-estar influenciaram positivamente na adesão medicamentosa.


Objetivos: identificar las percepciones sobre el bienestar, apoyo social, intensidad de los síntomas y su impacto en las actividades diarias de pacientes con cánceres cerebrales y correlacionar los resultados con los niveles de adhesión a los quimioterápicos antineoplásicos orales. Método: estudio correlacional y transversal, realizado en un ambulatorio hospitalario universitario de São Paulo, Brasil, entre 2019 y 2020. Se utilizó un instrumento para la caracterización de la muestra y escalas específicas. Resultados: 26 participantes, mediana de 36,5 años, 61,5% sexo masculino, 53,9% diagnosticados con glioblastoma; 73,1% presentaron adhesión, red de apoyo social y índice alto de bienestar. El puntaje promedio de intensidad de los síntomas fue de bajo a medio, con peor puntuación para preocupación en el peor estado. La mayor adhesión se relacionó al apoyo afectivo, apoyo información, interacción social y apoyo emocional. Conclusión: la mayoría declaró niveles positivos de bienestar, apoyo social y pocos síntomas. La percepción de apoyo social y bienestar influyó positivamente en la adhesión medicamentosa.


Objectives: to identify perceptions about well-being, social support, intensity of symptoms and their impact on the daily activities of patients with brain cancers and correlate the findings with levels of adherence to oral antineoplastic chemotherapy. Method: correlational and cross-sectional study, conducted in a university hospital outpatient clinic in São Paulo, Brazil, between 2019 and 2020. An instrument was used to characterize the sample, in addition to specific scales. Results: 26 participants, median 36.5 years, 61.5% male, 53.9% diagnosed with glioblastoma; 73.1% showed adherence, social support network and high well-being index. The mean symptom intensity score was low to medium, with a worse score for worry in the worst state. Greater adherence was related to affective support, information support, social interaction and emotional support. Conclusion: most reported positive levels of well-being, social support and few symptoms. The perception of social support and well-being positively influenced drug adherence.


Asunto(s)
Humanos , Masculino , Femenino , Adolescente , Adulto , Persona de Mediana Edad , Anciano , Calidad de Vida , Apoyo Social , Correlación de Datos , Antineoplásicos/uso terapéutico , Estudios Transversales , Glioblastoma/psicología
7.
Chinese Journal of Biotechnology ; (12): 1477-1501, 2023.
Artículo en Chino | WPRIM | ID: wpr-981149

RESUMEN

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.


Asunto(s)
Humanos , Glioblastoma/genética , Exosomas/metabolismo , MicroARNs/metabolismo , Pronóstico , Proliferación Celular , Neoplasias Encefálicas/genética , Línea Celular Tumoral
8.
Journal of Integrative Medicine ; (12): 120-129, 2023.
Artículo en Inglés | WPRIM | ID: wpr-971656

RESUMEN

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.


Asunto(s)
Humanos , Glioblastoma/patología , Endocannabinoides/uso terapéutico , Neoplasias Encefálicas/patología , Proliferación Celular , Línea Celular Tumoral , Cannabinoides/uso terapéutico
9.
Protein & Cell ; (12): 105-122, 2023.
Artículo en Inglés | WPRIM | ID: wpr-971612

RESUMEN

Glioblastoma multiforme (GBM), a highly malignant and heterogeneous brain tumor, contains various types of tumor and non-tumor cells. Whether GBM cells can trans-differentiate into non-neural cell types, including mural cells or endothelial cells (ECs), to support tumor growth and invasion remains controversial. Here we generated two genetic GBM models de novo in immunocompetent mouse brains, mimicking essential pathological and molecular features of human GBMs. Lineage-tracing and transplantation studies demonstrated that, although blood vessels in GBM brains underwent drastic remodeling, evidence of trans-differentiation of GBM cells into vascular cells was barely detected. Intriguingly, GBM cells could promiscuously express markers for mural cells during gliomagenesis. Furthermore, single-cell RNA sequencing showed that patterns of copy number variations (CNVs) of mural cells and ECs were distinct from those of GBM cells, indicating discrete origins of GBM cells and vascular components. Importantly, single-cell CNV analysis of human GBM specimens also suggested that GBM cells and vascular cells are likely separate lineages. Rather than expansion owing to trans-differentiation, vascular cell expanded by proliferation during tumorigenesis. Therefore, cross-lineage trans-differentiation of GBM cells is very unlikely to occur during gliomagenesis. Our findings advance understanding of cell lineage dynamics during gliomagenesis, and have implications for targeted treatment of GBMs.


Asunto(s)
Ratones , Animales , Humanos , Glioblastoma/patología , Células Endoteliales/patología , Variaciones en el Número de Copia de ADN , Encéfalo/metabolismo , Neoplasias Encefálicas/patología
10.
Journal of Zhejiang University. Science. B ; (12): 32-49, 2023.
Artículo en Inglés | WPRIM | ID: wpr-971467

RESUMEN

Hypoxia, as an important hallmark of the tumor microenvironment, is a major cause of oxidative stress and plays a central role in various malignant tumors, including glioblastoma. Elevated reactive oxygen species (ROS) in a hypoxic microenvironment promote glioblastoma progression; however, the underlying mechanism has not been clarified. Herein, we found that hypoxia promoted ROS production, and the proliferation, migration, and invasion of glioblastoma cells, while this promotion was restrained by ROS scavengers N-acetyl-L-cysteine (NAC) and diphenyleneiodonium chloride (DPI). Hypoxia-induced ROS activated hypoxia-inducible factor-1α (HIF-1α) signaling, which enhanced cell migration and invasion by epithelial-mesenchymal transition (EMT). Furthermore, the induction of serine protease inhibitor family E member 1 (SERPINE1) was ROS-dependent under hypoxia, and HIF-1α mediated SERPINE1 increase induced by ROS via binding to the SERPINE1 promoter region, thereby facilitating glioblastoma migration and invasion. Taken together, our data revealed that hypoxia-induced ROS reinforce the hypoxic adaptation of glioblastoma by driving the HIF-1α-SERPINE1 signaling pathway, and that targeting ROS may be a promising therapeutic strategy for glioblastoma.


Asunto(s)
Humanos , Hipoxia de la Célula , Línea Celular Tumoral , Glioblastoma/patología , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Inhibidor 1 de Activador Plasminogénico/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal , Microambiente Tumoral , Neoplasias Encefálicas/patología
11.
China Journal of Chinese Materia Medica ; (24): 211-219, 2023.
Artículo en Chino | WPRIM | ID: wpr-970516

RESUMEN

Glioblastoma is the most common primary cranial malignancy, and chemotherapy remains an important tool for its treatment. Sanggenon C(San C), a class of natural flavonoids extracted from Morus plants, is a potential antitumor herbal monomer. In this study, the effect of San C on the growth and proliferation of glioblastoma cells was examined by methyl thiazolyl tetrazolium(MTT) assay and 5-bromodeoxyuridinc(BrdU) labeling assay. The effect of San C on the tumor cell cycle was examined by flow cytometry, and the effect of San C on clone formation and self-renewal ability of tumor cells was examined by soft agar assay. Western blot and bioinformatics analysis were used to investigate the mechanism of the antitumor activity of San C. In the presence of San C, the MTT assay showed that San C significantly inhibited the growth and proliferation of tumor cells in a dose and time-dependent manner. BrdU labeling assay showed that San C significantly attenuated the DNA replication activity in the nucleus of tumor cells. Flow cytometry confirmed that San C blocked the cell cycle of tumor cells in G_0/G_1 phase. The soft agar clone formation assay revealed that San C significantly attenuated the clone formation and self-renewal ability of tumor cells. The gene set enrichment analysis(GSEA) implied that San C inhibited the tumor cell division cycle by affecting the myelocytomatosis viral oncogene(MYC) signaling pathway. Western blot assay revealed that San C inhibited the expression of cyclin through the regulation of the MYC signaling pathway by lysine demethylase 4B(KDM4B), which ultimately inhibited the growth and proliferation of glioblastoma cells and self-renewal. In conclusion, San C exhibits the potential antitumor activity by targeting the KDM4B-MYC axis to inhibit glioblastoma cell growth, proliferation, and self-renewal.


Asunto(s)
Humanos , Glioblastoma/genética , Bromodesoxiuridina/uso terapéutico , Transducción de Señal , Proteínas Proto-Oncogénicas c-myc/metabolismo , Agar , Proliferación Celular , Línea Celular Tumoral , Apoptosis , Histona Demetilasas con Dominio de Jumonji/metabolismo
12.
Chinese Medical Journal ; (24): 4-12, 2023.
Artículo en Inglés | WPRIM | ID: wpr-970047

RESUMEN

Leucine-rich repeats containing 4 ( LRRC4 , also named netrin-G ligand 2 [NGL-2]) is a member of the NetrinGs ligands (NGLs) family. As a gene with relatively high and specific expression in brain, it is a member of the leucine-rich repeat superfamily and has been proven to be a suppressor gene for gliomas, thus being involved in gliomagenesis. LRRC4 is the core of microRNA-dependent multi-phase regulatory loops that inhibit the proliferation and invasion of glioblastoma (GB) cells, including LRRC4/NGL2-activator protein 2 (AP2)-microRNA (miR) 182-LRRC4 and LRRC4-miR185-DNA methyltransferase 1 (DNMT1)-LRRC4/specific protein 1 (SP1)-DNMT1-LRRC4. In this review, we demonstrated LRRC4 as a new member of the partitioning-defective protein (PAR) polarity complex that promotes axon differentiation, mediates the formation and plasticity of synapses, and assists information input to the hippocampus and storage of memory. As an important synapse regulator, aberrant expression of LRRC4 has been detected in autism, spinal injury and GBs. LRRC4 is a candidate susceptibility gene for autism and a neuro-protective factor in spinal nerve damage. In GBs, LRRC4 is a novel inhibitor of autophagy, and an inhibitor of protein-protein interactions involving in temozolomide resistance, tumor immune microenvironment, and formation of circular RNA.


Asunto(s)
Humanos , Línea Celular Tumoral , Glioblastoma/metabolismo , Leucina , Proteínas Repetidas Ricas en Leucina/genética , MicroARNs , Proteínas del Tejido Nervioso/genética , Microambiente Tumoral
13.
Arq. bras. neurocir ; 41(1): 14-18, 07/03/2022.
Artículo en Inglés | LILACS | ID: biblio-1362068

RESUMEN

Objectives The present study aims to categorize the prevalence of intracranial tumors surgically treated at the neurosurgery service of Hospital Universitário Evangélico Mackenzie (HUEM) between 2016 and 2018. Material and Methods This survey included patients surgically treated due to primary or metastatic intracranial neoplasia between 2016 and 2018 at a referral center in the city of Curitiba. These patients were analyzed for epidemiological, histopathological, and topographic data, and they underwent an assessment of the outcome at the time of hospital discharge. Results Atotal of 96patientsmet the inclusion criteria. Themost prevalent tumorwas the glioma, with 39.6% of the sample, with glioblastoma being themost prevalent histological type. Brainmetastases andmeningiomas represented, respectively, 21.9%and 18.8%of the total. There was a predominance of supratentorial and intra-axial tumors in our sample. Conclusion Glioma was the most commonly found tumor, directly associated with high morbidity and mortality. The development of new and more effective drugs with action directed at themolecular level of intracranial tumorsmay be the path to a longer survival and improvement in the quality of life of these patients.


Asunto(s)
Neoplasias Craneales/epidemiología , Neoplasias Supratentoriales/epidemiología , Glioblastoma/epidemiología , Metástasis de la Neoplasia/diagnóstico , Neoplasias Craneales/cirugía , Neoplasias Craneales/fisiopatología , Perfil de Salud , Registros Médicos , Estudios Retrospectivos , Interpretación Estadística de Datos , Glioblastoma/mortalidad
14.
Acta Academiae Medicinae Sinicae ; (6): 276-285, 2022.
Artículo en Chino | WPRIM | ID: wpr-927876

RESUMEN

Objective To investigate the relationship between the expression of glutathione peroxidase(GPX)genes and the clinical prognosis in glioma patients,and to construct and evaluate the model for predicting the prognosis of glioma. Methods The clinical information and GPX expression of 663 patients,including 153 patients of glioblastoma(GBM)and 510 patients of low-grade glioma(LGG),were obtained from The Cancer Genome Atlas(TCGA)database.The relationship between GPX expression and patient survival was analyzed.The key GPX affecting the prognosis of glioma was screened out by single- and multi-factor Cox's proportional-hazards regression models and validated by least absolute shrinkage and selection operator(Lasso)regression.Finally,we constructed the model for predicting the prognosis of glioma with the screening results and then used concordance index and calibration curve respectively to evaluate the discrimination and calibration of model. Results Compared with those in the control group,the expression levels of GPX1,GPX3,GPX4,GPX7,and GPX8 were up-regulated in glioma patients(all P<0.001).Moreover,the expression levels of other GPX except GPX3 were higher in GBM patients than in LGG patients(all P<0.001).The Kaplan-Meier curves showed that the progression-free survival of GBM with high expression of GPX1(P=0.013)and GPX4(P=0.040),as well as the overall survival,disease-specific survival,and progression-free survival of LGG with high expression of GPX1,GPX7,and GPX8,was shortened(all P<0.001).GPX7 and GPX8 were screened out as the key factors affecting the prognosis of LGG.The results were further used to construct a nomogram model,which suggested GPX7 was the most important variable.The concordance index of the model was 0.843(95%CI=0.809-0.853),and the calibration curve showed that the predicted and actual results had good consistency. Conclusion GPX7 is an independent risk factor affecting the prognosis of LGG,and the nomogram model constructed with it can be used to predict the survival rate of LGG.


Asunto(s)
Humanos , Neoplasias Encefálicas , Glioblastoma , Glioma/diagnóstico , Glutatión Peroxidasa/metabolismo , Peroxidasas , Pronóstico , Modelos de Riesgos Proporcionales
15.
Biomedical and Environmental Sciences ; (12): 419-436, 2022.
Artículo en Inglés | WPRIM | ID: wpr-927681

RESUMEN

Objective@#To investigate the function of primary cilia in regulating the cellular response to temozolomide (TMZ) and ionizing radiation (IR) in glioblastoma (GBM).@*Methods@#GBM cells were treated with TMZ or X-ray/carbon ion. The primary cilia were examined by immunostaining with Arl13b and γ-tubulin, and the cellular resistance ability was measured by cell viability assay or survival fraction assay. Combining with cilia ablation by IFT88 depletion or chloral hydrate and induction by lithium chloride, the autophagy was measured by acridine orange staining assay. The DNA damage repair ability was estimated by the kinetic curve of γH2AX foci, and the DNA-dependent protein kinase (DNA-PK) activation was detected by immunostaining assay.@*Results@#Primary cilia were frequently preserved in GBM, and the induction of ciliogenesis decreased cell proliferation. TMZ and IR promoted ciliogenesis in dose- and time-dependent manners, and the suppression of ciliogenesis significantly enhanced the cellular sensitivity to TMZ and IR. The inhibition of ciliogenesis elevated the lethal effects of TMZ and IR via the impairment of autophagy and DNA damage repair. The interference of ciliogenesis reduced DNA-PK activation, and the knockdown of DNA-PK led to cilium formation and elongation.@*Conclusion@#Primary cilia play a vital role in regulating the cellular sensitivity to TMZ and IR in GBM cells through mediating autophagy and DNA damage repair.


Asunto(s)
Humanos , Antineoplásicos Alquilantes/uso terapéutico , Neoplasias Encefálicas/metabolismo , Línea Celular Tumoral , ADN/uso terapéutico , Glioblastoma/metabolismo , Radiación Ionizante , Temozolomida/uso terapéutico
16.
Arq. bras. neurocir ; 40(4): 368-373, 26/11/2021.
Artículo en Inglés | LILACS | ID: biblio-1362105

RESUMEN

Glioblastoma multiforme (GBM) is the most frequent and most aggressive primary brain tumor in adults,mainly located in the cerebral hemispheres. In the literature, few cases of primary GBM have been reported to have radiographic and intraoperative features of extra-axial lesions, leading to a diagnostic dilemma. Despite the advances in imaging modalities, the diagnosis of GBM can be challenging, and it is mainly based on the histopathologic confirmation of the excised tumor. We describe the case of a 76- year-old previously healthy female patient who presented to our hospital due to speech disturbances and cognitive impairment. The diagnosis of the tumor type on magnetic resonance imaging (MRI) was difficult, as the findings were suggestive of a malignant meningioma due to the heterogeneous enhancement of a dural-based mass with a dural tail sign. Moreover, the intraoperative findings revealed an extra-axial mass attached to the dura. A histological examination confirmed the diagnosis of glioblastoma with arachnoid infiltration. The patient underwent adjuvant radiotherapy and concomitant temozolomide treatment, she had clinical improvement postoperatively, and was stable during the six months of follow-up. Glioblastoma should be considered in the differential diagnosis of primary extra-axial mass with atypical and malignant features, especially in elderly patients.


Asunto(s)
Humanos , Femenino , Anciano , Neoplasias Encefálicas/terapia , Glioblastoma/radioterapia , Glioblastoma/terapia , Aracnoides , Neoplasias Encefálicas/diagnóstico por imagen , Glioblastoma/patología , Glioblastoma/diagnóstico por imagen , Diagnóstico Diferencial , Temozolomida/uso terapéutico
17.
Rev. cuba. med ; 60(4)dic. 2021.
Artículo en Español | LILACS, CUMED | ID: biblio-1408943

RESUMEN

Introducción: El glioblastoma multiforme es el tumor cerebral primario más frecuente y agresivo en adultos, representa cerca de 25 por ciento de los tumores intracraneales. Las principales manifestaciones clínicas están dadas por cefalea, convulsiones, cambios de conducta y un síndrome focal más definido (frontal, temporal, parietooccipital o del cuerpo calloso). En algunos pacientes, el comienzo es brusco por hemorragia o crecimiento rápido de un quiste intratumoral. El diagnóstico se realiza por resonancia magnética y se confirma con biopsia cerebral. El tratamiento es multidisciplinario e incluye resección quirúrgica, quimioterapia y radioterapia. No obstante, el pronóstico es desfavorable en la mayor parte de los pacientes. Objetivo: Describir el caso de un paciente con glioblastoma multiforme que se presentó en forma seudovascular. Caso clínico: Se presenta el caso de un paciente masculino de 60 años de edad con antecedentes de hipertensión arterial y enfermedad cerebrovascular. Tres días antes de su ingreso comenzó a manifestar dificultad para hablar y alteración en la marcha por pérdida de la fuerza muscular en el hemicuerpo derecho. Por lo anteriormente expuesto fue llevado al Hospital Clínico Quirúrgico Julio Trigo López donde fue ingresado y se diagnosticó un tumor cerebral. El paciente evolucionó tórpidamente y falleció. El estudio anatomopatológico arrojó la presencia de un glioblastoma multiforme. Conclusiones: El caso presentado de glioblastoma multiforme forma de defecto motor ofrece información sobre esta afección que en nuestro centro no es habitual(AU)


Introduction: Glioblastoma multiforme is the most frequent and aggressive primary brain tumor in adults, representing about 25percent of intracranial tumors. The main clinical manifestations are given by headache, seizures, behavior changes and a more defined focal syndrome (frontal, temporal, parieto-occipital or corpus callosum). In some patients, the onset is abrupt due to bleeding or rapid growth of an intratumoral cyst. The diagnosis is made by magnetic resonance imaging and confirmed with brain biopsy. Treatment is multidisciplinary and it includes surgical resection, chemotherapy, and radiation therapy. However, the prognosis is poor in most patients. Objective: To describe the case of a patient with glioblastoma multiforme that presented in a pseudovascular form. Clinical report: The case of a 60-year-old male patient with a history of arterial hypertension and cerebrovascular disease is report. Three days before his admission, he began to show difficulty speaking and gait disturbance due to loss of muscle strength in the right half of his body. For the foregoing, he was taken to Julio Trigo López Surgical Clinical Hospital where he was admitted and diagnosed with a brain tumor. The patient evolved torpidly and died. The pathological study revealed the presence of a glioblastoma multiforme. Conclusions: The reported case of glioblastoma multiforme in the form of a motor defect provides information on this condition that is not common in our center(AU)


Asunto(s)
Humanos , Masculino , Persona de Mediana Edad , Biopsia/métodos , Neoplasias Encefálicas/cirugía , Espectroscopía de Resonancia Magnética/métodos , Glioblastoma/diagnóstico por imagen
18.
MedUNAB ; 24(3): 359-364, 202112.
Artículo en Español | LILACS | ID: biblio-1353578

RESUMEN

Introducción. El xantoastrocitoma pleomórfico es una lesión glial de bajo grado de malignidad (grado II), puede presentar transformación maligna progresando a xantoastrocitoma pleomórfico anaplásico o glioblastoma multiforme, clasificados en grado III y IV, respectivamente, de acuerdo con la OMS. El glioblastoma epitelioide es un subtipo morfológico poco común del glioblastoma, de comportamiento agresivo, asociado a recurrencia temprana y compromiso leptomeníngeo. Presentación del caso. Se describe un reporte de caso de paciente femenina de 13 años con hallazgos de xantoastrocitoma pleomórfico anaplásico asociado a glioblastoma epitelioide, neoplasia poco frecuente que suele presentarse en la población pediátrica y en los adultos jóvenes. Discusión. El diagnóstico de glioblastoma epitelioide constituye un desafío, solo se han reportado unas pocas series pequeñas en la población adulta y pediátrica. Conclusión. Los hallazgos imagenológicos en las dos entidades son similares y comparten características histopatológicas e incluso algunos hallazgos moleculares superpuestos, lo cual dificulta su diferenciación, por lo que continúa siendo de gran controversia si se presentan conjuntamente o si el xantoastrocitoma pleomórfico anaplásico es un precursor del glioblastoma epitelioide.


Introduction. Pleomorphic xanthoastrocytoma is a glial lesion with low grade of malignancy (grade II), it can present malignant transformation progressing to anaplastic pleomorphic xanthoastrocytoma or glioblastoma multiforme, classified as grade III and IV, respectively, according to the WHO. Epithelioid glioblastoma is a rare morphological subtype of glioblastoma, with aggressive behavior, associated with early recurrence and leptomeningeal compromise. Case Presentation. Case report of a 13-year-old female patient with findings of anaplastic pleomorphic xanthoastrocytoma associated with epithelioid glioblastoma, a rare neoplasm that usually occurs in the pediatric population and in young adults. Discussion. The diagnosis of epithelioid glioblastoma is challenging, only a few small series have been reported in the adult and pediatric population. Conclusion. The imaging findings in the two entities are similar and share histopathological characteristics and even some overlapping molecular findings, which makes their differentiation difficult. For this reason, there is still a great controversy whether these entities are present continuously or whether the anaplastic pleomorphic xanthoastrocytoma is a precursor of epithelioid glioblastoma.


Introdução. O xantoastrocitoma pleomórfico é uma lesão glial de baixo grau de malignidade (grau II), pode apresentar transformação maligna progredindo para xantoastrocitoma pleomórfico anaplásico ou glioblastoma multiforme, classificados como grau III e IV, respectivamente, de acordo com a OMS. O glioblastoma epitelióide é um subtipo morfológico raro de glioblastoma, com comportamento agressivo, associado a recorrência precoce e envolvimento leptomeníngeo. Apresentação do caso. É descrito um relatório de caso de uma paciente feminina de 13 anos com achados de xantoastrocitoma pleomórfico anaplásico associado ao glioblastoma epitelióide, uma neoplasia rara que geralmente ocorre na população pediátrica e em adultos jovens. Discussão. O diagnóstico do glioblastoma epitélioide é desafiador, apenas algumas pequenas séries foram reportadas na população adulta e pediátrica. Conclusão. As descobertas imagiológicas nas duas entidades são semelhantes e compartilham características histopatológicas e, até mesmo, algumas descobertas moleculares sobrepostas, o que dificulta sua diferenciação, portanto permanece controverso se ocorrem juntas ou se o xantoastrocitoma pleomórfico anaplásico é um precursor do glioblastoma epitélioide.


Asunto(s)
Neoplasias Encefálicas , Astrocitoma , Glioblastoma , Diagnóstico Diferencial , Glioma
19.
Rev. colomb. anestesiol ; 49(3): e600, July-Sept. 2021. tab, graf
Artículo en Inglés | LILACS, COLNAL | ID: biblio-1280183

RESUMEN

Abstract Tuberous sclerosis (TSC) is a rare disease with multi-systemic involvement, predominantly neurological. Little evidence exists about the anesthetic management of patients with this disorder, particularly in pregnant women. This article discusses a case of a patient with TSC admitted to our hospital for the delivery of a twin gestation. Twenty-four hours after surgery, the patient presented left-side facial-brachial hypoesthesia and headache. A brain CT revealed a right frontal cortical bleeding tumor, which was diagnosed as glioblastoma multiforme. The patient was discharged 15 days after admission and a neurosurgical approach was suggested.


Resumen La esclerosis tuberosa es una enfermedad poco frecuente asociada con compromiso multisistémico, principalmente neurológico. Es poca la evidencia sobre el manejo anestésico de los pacientes con este trastorno, en particular las mujeres embarazadas. En este artículo presentamos el caso de una paciente con esclerosis tuberosa ingresada en nuestro hospital para el parto de una gestación gemelar. Veinticuatro horas después de la cirugía, la paciente presentó hipoestesia facial y braquial izquierda y cefalea. La tomografía cerebral mostró un tumor cortical sangrante en el lóbulo frontal derecho, diagnosticado como glioblastoma multiforme. La paciente fue dada de alta 15 días después de su ingreso y, con recomendación de manejo por neurocirugía.


Asunto(s)
Humanos , Femenino , Embarazo , Cesárea , Glioblastoma , Cefalea , Anestesia Epidural , Anestésicos , Neurocirugia , Esclerosis Tuberosa , Encéfalo , Enfermedades Raras , Parto , Hemorragia , Hospitales , Hipoestesia , Neoplasias , Enfermedades del Sistema Nervioso
20.
Arq. bras. neurocir ; 40(3): 284-287, 15/09/2021.
Artículo en Inglés | LILACS | ID: biblio-1362168

RESUMEN

The COVID-19 pandemic has affected a large number of patients in all countries, overwhelming healthcare systems worldwide. In this scenario, surgical procedures became restricted, causing unacceptable delays in the treatment of certain pathologies, such as glioblastoma. Regarding this tumor with high morbidity and mortality, early surgical treatment is essential to increase the survival and quality of life of these patients. Association between COVID-19 and neurosurgical procedures is quite scarce in the literature, with a few reported cases. In the present study, we present a rare case of a patient undergoing surgical resection of glioblastoma with COVID-19.


Asunto(s)
Humanos , Masculino , Anciano , Neoplasias Encefálicas/cirugía , Glioblastoma/cirugía , COVID-19/tratamiento farmacológico , Neoplasias Encefálicas/diagnóstico por imagen , Resultado del Tratamiento , Glioblastoma/patología , Glioblastoma/diagnóstico por imagen , Procedimientos Neuroquirúrgicos/métodos
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