RESUMO
Glioblastoma multiforme (GBM) is the most lethal and aggressive primary brain tumor. Several other abnormalities (neoplastic, infectious, or vascular) can mimic symptoms seen with GBM. This article reviews GBM and presents a case study that demonstrates the rationale for biopsy and pathologic diagnosis prior to the initiation of treatment for malignant brain tumors.
Assuntos
Glioblastoma/patologia , Idoso , Biópsia , Glioblastoma/diagnóstico , Glioblastoma/terapia , Humanos , MasculinoRESUMO
BACKGROUND: Senescence-associated genes (SAGs) are responsible for the senescence-associated secretory phenotype, linked in turn to cellular aging, the aging brain, and the pathogenesis of cancer. OBJECTIVE: We hypothesized that senescence-associated genes are overexpressed in older patients, in higher grades of glioma, and portend a poor prognosis. METHODS: Forty-seven gliomas were arrayed on a custom version of the Affymetrix HG-U133+2.0 GeneChip, for expression of fourteen senescence-associated genes: CCL2, CCL7, CDKN1A, COPG, CSF2RB, CXCL1, ICAM-1, IGFBP-3, IL-6, IL-8, SAA4, TNFRSF-11B, TNFSF-11 and TP53. A combined "senescence score" was generated using principal component analysis to measure the combined effect of the senescence-associated gene signature. RESULTS: An elevated senescence score correlated with older age (r=0.37; P=.01) as well as a higher degree of malignancy, as determined by WHO, histological grade (r=0.49; P<.001). There was a mild association with poor prognosis (P=.06). Gliosarcomas showed the highest scores. Six genes independently correlated with either age (IL-6, TNFRSF-11B, IGFBP-3, SAA4, and COPG), prognosis (IL-6, SAA4), or the grade of the glioma (IL-6, IL-8, ICAM-1, IGFBP-3, and COPG). CONCLUSION: We report: 1) a novel molecular signature in human gliomas, based on cellular senescence, translating the concept of SAG to human cancer; 2) the senescence signature is composed of genes central to the pathogenesis of gliomas, defining a novel, aggressive subtype of glioma; and 3) these genes provide prognostic biomarkers, as well as targets, for drug discovery and immunotherapy.
Assuntos
Envelhecimento/genética , Neoplasias Encefálicas/genética , Senescência Celular/genética , Progressão da Doença , Regulação Neoplásica da Expressão Gênica/genética , Glioma/genética , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Encéfalo , Neoplasias Encefálicas/patologia , Feminino , Glioma/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Análise de Sequência com Séries de Oligonucleotídeos/métodos , Análise de Componente Principal , Prognóstico , Índice de Gravidade de Doença , Análise de SobrevidaRESUMO
BACKGROUND: Merkel cell carcinoma (MCC) is a rare, highly malignant, and aggressive dermal neuroendocrine neoplasm that rarely metastasizes to the central nervous system. OBJECTIVE: To review the current literature regarding treatment of neurometastatic MCC. METHODS: A case of a 78-year-old male with intracranial extra-axial metastatic MCC involving the left cerebellopontine angle is presented. RESULTS: A retrosigmoid craniectomy was performed with complete resection of the metastatic focus. Adjuvant treatment included whole-brain radiation therapy followed by etoposide and carboplatin chemotherapy. Seven months postoperatively, the patient was free of metastatic disease. CONCLUSION: Surgical resection should be performed when feasible to prevent local recurrence. This may be followed by early adjuvant fractionated whole-brain radiotherapy and systemic chemotherapy; however, no clinical trials have been performed to demonstrate a survival benefit.
Assuntos
Carcinoma de Célula de Merkel/secundário , Neoplasias Cerebelares/secundário , Ângulo Cerebelopontino/patologia , Neoplasias Cutâneas/patologia , Idoso , Antineoplásicos Fitogênicos/administração & dosagem , Carboplatina/administração & dosagem , Carcinoma de Célula de Merkel/cirurgia , Ângulo Cerebelopontino/cirurgia , Quimioterapia Adjuvante , Craniotomia , Etoposídeo/administração & dosagem , Humanos , Masculino , Dosagem Radioterapêutica , Radioterapia Adjuvante , Neoplasias Cutâneas/cirurgiaRESUMO
The role of neural stem cells in gliomagenesis remains controversial. The aim of this study was to determine the anatomic relationship of human gliomas to the lining of the ventricular walls, known as the subventricular zone, an area replete with neural stem cells. We performed a retrospective radiographic analysis of 100 consecutive patients with gliomas and sought to determine the relationship of the lesions to the ventricular walls as seen on their MRI scans. Our results indicated that in 93% of cases the lesions contacted at least one region of the lateral ventricular wall. Contact with the ventricular wall was independent of the glioma size or mass effect. These findings were correlated to cytoarchitectural studies of the human subventricular zone. Our findings lend further support that there is an intimate association between gliomas and the subventricular zone.
