Roberto Assietti

Multiple meningiomas: A clinical, surgical, and cytogenetic analysis

Eight cases of multiple meningiomas were found in our 13-year series of 148 operated meningiomas. The relative frequency, 5.4%, of multiple meningiomas observed is compared with that in the literature. The clinical presentation, surgical results, and diagnostic tools are discussed. Cytogenetic analysis was performed in five patients (eight neoplastic specimens). No specific abnormality for multiple meningiomas was found, but our results point out the different origin of each tumor and exclude cell migration through the subarachnoid space as a pathogenetic factor in multiple meningiomas.

Chemotherapy for malignant gliomas of the brain: a review of ten-years experience

SummaryIn recent years, there has been a great improvement in the knowledge of the biological aspects of malignant gliomas of the brain. Conversely, there has been an increase of interest in the multimodal treatment of these tumours.In this review, we have analyzed the results of the several reports which have appeared in the literature that deal with the chemotherapeutic treatment of malignant gliomas. Furthermore, some areas of biological investigation that could have an impact on pharmacological therapy are discussed.

Cell-Kinetic Characteristics of Human Brain Tumors

The proliferative potential of human brain tumors was investigated, in vivo, using bromodeoxyuridine (BUDR) incorporation and flow cytometry (FCM). Patients with a variety of human brain tumors were preoperatively injected with 250 mg of BUDR intravenously. The cell cycle parameters of most of the specimen were measured within 24 h of sampling. The results show that this method is very practical, fast, and feasible for determining the cell-kinetic parameters of human brain tumors. In this study important kinetic parameters such as the duration of S-phase and the potential doubling time of each tumor were calculated in some samples. Our results show a significant difference in labelling index between meningiomas and gliomas. No difference between benign and anaplastic meningiomas was demonstrated in this limited number of cases. The correlation between the labelling index and the clinical and radiological follow-up of each patient should make the assessment of the prognostic significance of the kinetic evaluation, possible. This method could be a useful aid in the selection of new treatment schedules.

Hormonal modulation of brain tumour growth: a cell culture study

SummaryTissue samples derived from two neuroepithelial tumours and five meningiomas were obtained at surgery from seven patients and cultured in order to study the effect of dexamethasone (DEX) and testosterone acetate (TA) on cell proliferation.Glucocorticoid and androgen receptors (GR, AR) were determined both on tissue samples (7 cases) and on five out of the seven cell cultures obtained by tumours.GR and AR were present respectively in 5 and in 4 out of the tumour specimens assayed and in 4/5 and 2/3 of the tested cell cultures.DEX activity on cell growth was tested on six cell cultures. Four of them showed a significant growth inhibition at the highest drug concentration. On the contrary, a significant growth stimulation was observed in four out of the five cultures, where GR were present, using low hormone concentrations. Treatment with pharmacological doses of TA caused a significant cytotoxicity in all the tested cultures. Low TA concentrations inhibited cell growth in one out of the two cell cultures which contained AR, but were ineffective in cultures lacking AR.Our preliminary results suggest a possible role in growth regulation by DEX and TA in intracranial tumours, on the basis of the presence of specific hormone receptors.

A study on the biological behavior of human brain tumors Part I. Arachidonic acid metabolism and DNA content

SummaryThe study of proliferative characteristics and biochemical aspects seem to be of great importance in order to define brain neoplastic behavior.The purpose of this study is to verify the existence of any possible correlation between Arachidonic Acid (AA) metabolism and proliferative characteristics in 30 meningiomas and 30 neuroepithelial tumors. The most represented metabolite in neuroepithelial tumors is TxB2, while 6-Keto-PGF1α is the lowest represented product. Unimodal DNA distribution was observed in 66% of neuroepithelial tumors and in 87% of meningiomas. Aneuploidy was more frequent in glioblastomas and anaplastic meningiomas as previously reported; AA overall synthesis capacity and profile were similar between unimodal and bimodal cases of neuroepithelial tumors. Total AA metabolite, as well as TxB2 and PGD2, synthesis capacity are significantly higher in cases with S-phase cell percentage ≥ 3% than in cases with S-phase % < 3%.Total production of AA metabolites via the cyclooxygenase pathway is significantly higher in meningiomas with bimodal DNA distribution than in cases with unimodal DNA content; when considering S-phase cell percentage, similarly to what observed in neuroepithelial tumors, meningiomas with S% > 3% shows a significantly higher overall synthesis capacity for AA. AA metabolism capacity well correlates with proliferative patterns in neuroepithelial tumors: the relationship depends preferentially on TxB2 and PGD2 synthesis capacity. In cases of meningiomas, the amount of AA metabolites seem to be related to DNA content and proliferative activity when anaplastic features are histologically demonstrated.

A study on the biological behavior of human brain tumors Part II: Steroid receptors and arachidonic acid metabolism

SummaryThe significance of steroid receptors (SR) in human brain tumors is presently a field of intense investigation in order to clarify some aspects of the biological behavior of these neoplasms. We studied the relationship between the presence of steroid receptors and the production of metabolites of the arachidonic acid cascade which have been reported to have a role in the biological behavior of some human tumors. We found that some metabolites of arachidonic acid are produced in different amounts in brain tumors which either did or did not express some steroid receptors. In particular the PGE2 were higher in estrogen receptors (ER) positive meningiomas than in ER negative ones and 6-keto-PGF1α, the stable metabolite of prostacyclin, is significantly higher in androgen receptors (AR) negative meningiomas than in AR positive ones. In neuroepithelial tumors the glucocorticoid receptors (GR) positive cases synthesized more TxB2 and less PGE2 than the GR negative ones. Our data seem to suggest that some correlations exist between the presence of some steroid receptors and arachidonic acid metabolite production.

Early or Late Surgery for Supratentorial Gliomas? A Randomized Study

The purpose of this study was to determine the value of sequential radiotherapy followed by cytoreductive surgery as compared with cytoreductive surgery followed by radiotherapy and chemotherapy in supratentorial malignant gliomas in adults. Since 1978 forty-seven patients were entered into this study and were randomly submitted to surgical procedure (early or late), whole-brain irradiation (6000 cGy) and chemotherapy with BCNU (80 mg/sqm/ iv × 3 days). Twenty-five patients were assigned to the control arm (early surgery) and 22 to the late surgery arm. The results demonstrate no statistical difference in survival or in recurrence time between patients treated with early or late surgery. Toxicity was similar among the two groups but late-surgery patients had a better quality of life. Late surgical procedure appears safe and feasible. The tumor was often necrotic and well demarcated from surrounding brain and therefore often easily removed. Late surgery might be a treatment of choice for tumors with poor surgical indications.

CELLULAR LOCALIZATION OF GLUCOCORTICOID RECEPTOR mRNAs IN HUMAN CNS TUMORS BY IN SITU HYBRIDIZATION

Glucocorticoid hormone high affinity binding activity has been demonstrated in human brain tumor cell extracts by radiolabelled ligand assay. To determine the molecular species responsible for this activity and their cellular distribution, we studied by in situ hybridization, with a human glucocorticoid receptor (hGR) cDNA digoxigenin probe, the expression of hGR mRNA in 10 brain tumors (3 astrocytomas, 1 glioblastoma, 1 neurinoma, 3 meningiomas, 1 choroid plexus papilloma, 1 ependymoma). All tumors, with the exception of the glioblastoma and one fibroblastic meningiomas, contained hGR positive neoplastic cells. The intensity of positivity varied between different tumors and within the same tumor. These results indicate, for the first time, the presence of true hGR receptor mRNA in human brain tumor cells.