Systemic dissemination of glioblastoma: literature review

SUMMARY INTRODUCTION: Glioblastoma (GBM) is the most frequent primary malignant tumor from the central nervous system in adults. However, the presence of systemic metastasis is an extremely rare event. The objective of this study was to review the literature, evaluating the possible biological mechanisms related to the occurrence of systemic metastasis in patients diagnosed with GBM. RESULTS: The mechanisms that may be related to GBM systemic dissemination are the blood-brain barrier breach, often seen in GBM cases, by the tumor itself or by surgical procedures, gaining access to blood and lymphatic vessels, associated with the acquisition of mesenchymal features of invasiveness, resistance to the immune mechanisms of defense and hostile environment through quiescence. CONCLUSIONS: Tumor cells must overcome many obstacles until the development of systemic metastasis. The physiologic mechanisms are not completely clear. Although not fully understood, the pathophysiological understanding of the mechanisms that may be associated with the systemic spread is salutary for a global understanding of the disease. In addition, this knowledge may be used as a basis for a therapy to be performed in patients diagnosed with GBM distant metastasis.

RESUMO INTRODUÇÃO: Glioblastoma (GBM) é o tumor maligno mais comum do sistema nervoso central em adultos. Entretanto, metástase a distância de GBM é um evento extremamente raro. O presente estudo teve o objetivo de realizar uma revisão da literatura para avaliar os possíveis mecanismos biológicos relacionados com a ocorrência de metástase a distância de pacientes com diagnóstico de GBM. RESULTADOS: Os mecanismos que podem estar relacionados com a capacidade de disseminação sistêmica do GBM são a quebra de barreira hematoencefálica (BHE) frequentemente vista em GBM, seja pela doença, seja por procedimentos cirúrgicos, dando acesso aos vasos sanguíneos e linfáticos, associada à aquisição de características mesenquimais de invasividade, resistência aos mecanismos de defesa do sistema imunológico e adaptação a hostilidades dos meios distantes por meio de quiescência. CONCLUSÕES: As células tumorais necessitam vencer diversos obstáculos até a formação de uma metástase distante. Apesar de não totalmente esclarecido, o entendimento fisiopatológico dos mecanismos pelos quais podem estar associados à disseminação sistêmica do GBM é salutar para a compreensão global da doença. Além disso, esse conhecimento pode servir de base para a terapia a ser empregada diante do paciente com diagnóstico de GBM com metástase a distância.

Xenograft transplantation of human malignant astrocytoma cells into immunodeficient rats: an experimental model of glioblastoma

INTRODUCTION: Astrocytic gliomas are the most common intracranial central nervous system neoplasias, accounting for about 60 percent of all primary central nervous system tumors. Despite advances in the treatment of gliomas, no effective therapeutic approach is yet available; hence, the search for a more realistic model to generate more effective therapies is essential. OBJECTIVE: To develop an experimental malignant astrocytoma model with the characteristics of the human tumor. METHOD: Primary cells from subcutaneous xenograft tumors produced with malignant astrocytoma U87MG cells were inoculated intracerebrally by stereotaxis into immunosuppressed (athymic) Rowett rats. RESULTS: All four injected animals developed non-infiltrative tumors, although other glioblastoma characteristics, such as necrosis, pseudopalisading cells and intense mitotic activity, were observed. CONCLUSION: A malignant astrocytoma intracerebral xenograft model with poorly invasive behavior was achieved in athymic Rowett rats. Tumor invasiveness in an experimental animal model may depend on a combination of several factors, including the cell line used to induce tumor formation, the rat strains and the status of the animal's immune system.

Componente oligodendroglial e neuronal em glioblastomas: possível relação com o prognóstico / Oligodendroglial and neuronal component in glioblastomas: possible relation with prognosis

Glioblastomas são tumores astrocíticos de alto grau de malignidade e o diagnóstico baseado nos critérios histológicos atuais não tem explicado a maior sobrevida observada em alguns casos. A presença de um componente oligodendroglial foi proposta mais recentemente como um possível indicador de maior sobrevida, tanto pela OMS quanto pela classificação de Sainte Anne 2000. Esta última propõe ainda que um componente neuronal está relacionado com maior sobrevida. O objetivo deste estudo foi rever tumores de 40 pacientes diagnosticados como glioblastomas pelos critérios da OMS, com o propósito de identificar: a presença de um componente oligodendroglial utilizando critérios morfológicos; a presença de um componente neuronal utilizando marcadores imuno-histoquímicos (anticorpos anti-neurofilamento e sinaptofisina). Objetivou-se também correlacionar os achados histológicos e imuno-histoquímicos com a sobrevida dos pacientes, estudando também outras variáveis que podem ter influência na sobrevida. Foram identificados 11 tumores com componente oligodendroglial e 7 com componente neuronal. Apesar do pequeno número de casos estudados, a presença de um componente oligodendroglial associou-se com maior sobrevida. O valor da expressão de marcadores neuronais em gliomas malignos precisa ser confirmado com a avaliação de séries maiores.

Familial cancer: depressed NK-cell cytotoxicity in healthy and cancer affected members

Depressed natural killer (NK) cell activity has been showed in family members of patients with different types of cancer. The present work aimed to evaluate T cell subsets and NK cell cytotoxic activity in 15 members of a family with high incidence of tumors, such as glioblastoma, gastric, pancreas and colon rectal carcinoma, chronic myelocitic leukemia, melanoma and osteoblastoma. As controls, 19 healthy subjects with the age range equivalent were studied. The enumeration of CD3+ lymphocytes and their CD4+ and CD8+ subsets were defined by monoclonal antibodies and NK cell cytotoxicity towards K562 target cells were evaluated by single cell-assay. The results showed in family members low percentage of total T cells (CD3+), and their CD4+ subset and impairment of CD4/CD8 ratio in relation to control group. All family members presented percentage of NK-target cell conjugate formation bellow the minimum value observed in control group. Thirteen people were examined and followed up during five years, in order to assure that there was no undiagnosed or unsuspected disease at the moment of evaluation. One of them developed osteoblastoma and other malignant melanoma. Two cancer patients, with glioblastoma and chronic myelocytic leukemia were studied during illness. All the corresponding values were comparable. The persistence of low percentage of conjugate formation may be related to a defect on adhesion molecules expression in the surface of NK cells that was probably responsible for the low activity of these cells presented by the family group. Thus, the inheritance mechanism of low adherence of NK cells should have a prognostic value in determining the risk of developing tumors