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.

Oxidant/antioxidant status and immunoglobulin levels in patients with primary brain tumors before and after surgical intervention

To assess serum level of malondialehyde [MDA], total antioxidant status [TAS] as a representative of oxidative stress, with immunoglobulin levels [IgG, IgA, IgM] in patients with primary brain tumors at diagnosis and one month after surgical resection in comparison to healthy controls. The study was conducted in Iben-Seena Hospital in Mosul city Iraq. Thirty-seven patients with primary brain tumors were included in the study, later proved by histopathology to be cases of meningioma [24 cases] and glioma [13 cases]. Also included 32 apparently healthy, age and sex matched subjects as a control group. Initially, blood samples were taken from both the patients and controls and assessment of serum MDA, TAS and immunoglobulin levels [IgG, IgA, IgM] were done, later for the patients group one month after surgical resection of the tumor another blood samples were taken and assessment of the same parameters mentioned above were done again. Serum MDA was found to be significantly higher [p<0.001] and serum TAS was significantly lower [p<0.001] in patients with primary brain tumors [both meningioma and glioma] prior to surgical resection in comparison to controls. Postoperatively, there was a significant reduction [p<0.001] in serum MDA levels with an increase in TAS [which was slightly significant in gliomas and insignificant with meningiomas]. With regard to serum immunoglobulin levels, there was a significant increase in serum IgG [gliomas p<0.05; meningioma p<0.001] preoperatively compared with controls, with a significant reduction [p<0.001] in the serum levels of IgG, IgA and IgM postoperatively in comparison to preoperative values. Primary brain tumors [both meningioma and glioma] as a disease carry a substantial effects on oxidant/antioxidant status and on serum immunoglobulin levels as part of the humoral immunity so as the surgical removal of the tumor mass as a way of therapy

Imunoistoquímica em oligodendrogliomas / Immunohistochemstry in oligodendrogliomas

Os oligodendrogliomas (OL) são tumores gliais caracterizados histologicamente pela presença de núcleo redondo e homogêneo com halo claro perinuclear. A diferenciação microscópica desses tumores com neurocitoma central, DNT e algumas vezes com ependimoma de células claras pode ser difícil. O estudo imunoistoquímico com marcadores glial e neuronal tem sido utilizado e pode auxiliar no diagnóstico diferencial. O objetivo do presente estudo foi determinar a diferenciação neuronal e glial por meio de técnica imunoistoquímica utilizando anticorpos de rotina em tumores com características microscópicas de OL. Foram estudados 42 pacientes com idade entre 4 e 60 anos. Dez apresentavam sinais de maior malignidade (anaplásico). Trinta e três casos (78,5%) mostraram positividade para GFAP, sendo em 10 focal e 6 casos com expressão intensa. Doze casos (28,5%) apresentaram positividade para NSE e/ou sinaptofisina, demonstrando alguma diferenciação neuronal, principalmente focal. Trinta e quatro casos (80,9%) foram positivos para S-100 e três casos (7,1%) foram positivos focalmente para NeuN. Concluimos que áreas focais de diferenciação neuronal e/ou glial podem estar presente em OL típicos e, portanto, é necessário cautela no diagnóstico diferencial em amostras pequenas de tumor. A positividade difusa para marcadores neuronais deve sugerir o diagnóstico de neurocitoma central.

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.

Brain tumor inhibition in experimental model by restorative immunotherapy with a corpuscular antigen.

In view of the advances in our understanding of anti-tumor immune response, it is now tempting to contemplate the development of immunotherapies for malignant brain tumors, for which no effective treatment exists. Immunotherapy, with agents known as biological response modifiers (BRMs) are thus gaining increasing interest as the fourth modality of treatment. A non-specific BRM, sheep erythrocytes (SRBC) when administered (ip, 7% PCV/V, 0.5 ml) in a group of animals at the end of seventh month of ethylnitrosourea administration, resulted in significant increase in the mean survival time (> 350 days). Studies conducted for growth kinetics pattern with proliferation index and fluorochrome (HO-33342) uptake techniques at the tissue culture level exhibited a regulatory inhibition of the cells isolated from tissue excised from the tumor susceptible area of brain of SRBC treated animals. Moreover, histological examination of brain from animals showed immunomodulatory role of SRBC in experimentally induced brain tumor. Further probe into the mechanisms involving immunological investigations at the cellular level in these animals indicated an augmented and potentiated cell mediated immune response (CMI) as evidenced by enhanced spontaneous rosette forming capacity and cytotoxic activity of lymphocytes and neutrophil (PMN) mediated phagocytosis respectively. The observations suggest that SRBC down regulate malignant growth pattern of experimental brain tumors either by an immunologically enhanced killing of tumor cells and/or by directly inhibiting the tumor growth possibly via a stimulated cytokine network. Thus, a corpuscular antigen, can potentiate CMI response in experimentally induced brain tumor animal model, in which response induced in the periphery are able to mediate anti-tumor effects in the brain.

Anti-P53 antibodies in Brazilian brain tumor patients

Gliomas of astrocytic origin are the most common primary brain tumors, accounting for over 40 to 50 of all central nervous system tumors. The TP53 tumor suppressor gene is the most frequently mutated gene found in human malignancies. A mutation of this gene can lead to an increased half-life of the resulting protein and loss of biological function. High levels of p53 have been detected in the serum of colon cancer patients, although p53 protein has not been detected in the serum of brain tumor patients. Besides circulating p53, several studies have detected antibodies against p53 in patients with lung and breast cancer, as well as those with other types of cancer. We studied p53 protein and anti-p53 antibodies in the plasma of Brazilian brain tumor patients. Plasma samples were drawn from 24 untreated brain tumor patients and from 15 healthy donors without clinical signs of cancer. Western blotting techniques were used to detect p53 protein and anti-p53 antibodies. We found anti-p53 antibodies in 5/24 brain tumor patients. Age appears to affect the immune response, as four of six tumor patients under 16 years old had detectable anti-p53 antibodies, while these were found in only 1 of 18 adults (over 16 years old). We found no p53 protein in any of the serum samples from the brain tumors. Possibly the presence of this protein is affected by tumor type or by the organs that are sampled

Clinicopathological and immunological study of brain tumours at L.G.H. Lahore

Thirty one patients with different types of brain tumors at LGH Lahore were studied .Age, sex, ethnic background and date of diagnosis were recorded. Children below the age of 15 years were 30%. Preopendrance was notable. Most common syndromes were headache, cranial nerve involvement, vomiting, papilloedema and behavioural changes. Gliomas constitute 38%, followed by neurinoma 22%, medulloblastoma and meninginoma, CSF glucose, total protein, CSF cytology, abumin, I[g]G, I[g]A and I[g]M were setermined. CSF glucose was not affected, while total protein, albumin, I[g]G, I[g]A and I[g]M were higher in brain tumour. I[g]G and I[g]A were significantly higher in malignant tumours than benign ones. Increased concentraton of immunoglobulins in CSF suggest humor immune response of brain against neoplasm

Secretory meningioma: a case report with histopathological, immunohistochemical and ultrastructural analysis

Secretory meningioma have been described as a distinct variant of meningioma based on their histologic, immunohistochemical and ultrastructural features of epithelial and secretory differentiation of meningothelial cells with accumulation of secretory material in the form of hyaline inclusion. Secretory meningioma is also a benign tumor having similar biological behaviour to that of typical meningiomas: hence, it is important for it to be recognized and diagnosed correctly to avoid unnecessary radiation and chemotherapy. Here we present a case of secretory meningioma with typical morphologic features. The patient was a 56-year-old woman with bilateral visual disturbance. A well-circumscribed mass was present in the left frontal lobe of cerebrum with surrounding edema. The tumor was composed of whorls of meningothelial cells and abundant intra- and extracellular eosinophilic hyaline inclusions which showed immunoreactivity for epithelial membrane antigen(EMA) and carcinoembryonic antigen(CEA). Ultrastructural features also supported epithelial and secretory differentiation of tumor cells.