Biomedical subjects
Publications and source records attributed to R Roselli.
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Eleven cases of meningiomas were investigated for the presence of estrogen and progesterone receptors. These tumors specifically bound estradiol. This binding activity almost exclusively resulted from the presence of high numbers of type II estrogen binding sites (EBS). Estrogen receptors were absent or present at low concentrations. Competition analysis showed that the flavonoid, quercetin, competed for tritiated estradiol binding to type II EBS; both rutin and hesperidin did not. In addition, 10 microM quercetin, unlike rutin or hesperidin, was effective in inhibiting in vitro bromodeoxyuridine incorporation by meningioma cells. Although the mechanism of the antiproliferative activity of quercetin remains to be clarified, it is possible that this flavonoid may regulate cell growth through a ligand interaction with type II EBS.
A 'TGS' classification for supratentorial brain glioma is proposed, based on three parameters: tumour extension (T), histopathological grade (G) and extent of surgical resection (S). Two groups of patients were analysed: the first (n = 137) had tumour submitted to stereotactic biopsy; the second (n = 60) had malignant glioma operated on by craniotomy and tumor resection. All three staging parameters significantly influenced survival. Histopathological grade was the most significant factor, and the only independent variable on multivariate analysis, followed by extent of tumour and then extent of surgical resection. The data support the applicability of the proposed parameters for a staging classification of hemispheric brain glioma.
The preliminary results obtained in 19 patients treated with interstitial irradiation for malignant gliomas are reported. Three different groups are included in the study: I Newly diagnosed tumours not suitable for surgery: 13 cases (10 anaplastic astrocytomas (AA) and 3 glioblastomas (GBM), mean volume 46.56 cc, source Ir 192) were implanted permanently (n = 11, mean peripheral dose 93.54 Gy) or temporarily (n = 2, 50 Gy = 0.5 Gy/hr). External beam irradiation was additionally applied in all cases. II Residual or recurrent tumours: 5 patients (2 AA and 3 GBM, mean volume 7.2 cc, source Ir 192) received temporary implants (150 Gy peripheral dose = 1.5 Gy/hr) after surgery and conventional radiotherapy. III Newly diagnosed surgically removable tumours: only one patient with AA (15 cc volume, source Ir 192) received temporary implantation with the same dose regimen used in Group II before surgery and external beam irradiation. A median survival time of 26.75 mos (34.62 mos for AA, with 3 long-term survivors) was observed in the patients of Group I. Three patients of Group II are still alive after 8, 12 and 12 mos after brachytherapy, the other 2 (GBM) survived 7 and 12 mos. The single patient so far included in Group III is still alive after 6 mos. Although the study is still in progress, these preliminary data seem to indicate that interstitial radiotherapy can be effective in prolonging survival of patients with malignant gliomas.
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Thirteen patients suffering from severe partial epilepsy and potential candidates for surgical treatment were investigated with stereotactically implanted intracerebral electrodes during nocturnal physiological sleep. The recorded electrocerebral activity was automatically analyzed to gain information on interictal epileptic events during wakefulness and the phases of sleep. The interictal epileptic activity shows: (1) great variability in the different subjects, and intra-individually, variability according to the explored cerebral regions; (2) is not influenced by the location of the recorded epileptic events; and (3) is affected by the local level of epileptogenicity. The latter was determined by the assessment of the capacity to give origin to ictal discharges and the disappearance of seizures following surgical removal. The interictal rate of spiking from the most epileptogenic cerebral zone is characterized by a relative stability during the night and by a relatively high degree during REM sleep.
Tissue samples from 57 patients with neuroepithelial tumors (25 glioblastomas, 18 anaplastic astrocytomas, and 14 astrocytomas) were analyzed in order to evaluate the presence of estrogen, progesterone, glucocorticoid, and androgen receptors. Glucocorticoid- and androgen-specific binding proteins were present in 38.6% and 21.6% of the cases, respectively. Only a few tumors showed estrogen or progesterone receptors. A correlation was found between grade of anaplasia, patient's sex and age, and presence of glucocorticoid and androgen receptors. The biological role of these two receptors was investigated in 10 primary cell cultures derived from neuroepithelial tumors. For this purpose, dexamethasone and testosterone were added to culture medium at different concentrations (from 50 to 0.016 micrograms/ml). A significant stimulation of the cell growth was observed in four of five glucocorticoid receptor-positive cultures when dexamethasone in doses ranging from 2 to 0.016 microgram/ml was added to the culture. No modulation of the growth was observed in glucocorticoid receptor-negative cultures at the same doses. Higher dexamethasone doses induced a significant decrease of the growth index independently from the glucocorticoid receptor status. All of the cultures tested for testosterone activity were negative for androgen receptors. This hormone induced an inhibition of the growth index at doses ranging from 50 to 0.4 micrograms/ml. The data suggest that neuroepithelial tumors contain specific glucocorticoid and androgen binding proteins. Glucocorticoid receptors modulate the growth of cultured neuroepithelial tumors in the presence of different concentrations of dexamethasone.
Quantitative tumour growth into the brain (stage of the disease) and qualitative tumour evolution in the time (progression) are the two basic aspects of the natural history of the cerebral neoplastic disease. Recently the development of neuroradiological imaging (CT and MR) and the progress in biopathology of the nervous system tumours introduced new concepts like heterogeneity of neuroepithelial tumours or evolution to anaplasia. The findings obtained in 159 neuroepithelial tumours studied with stereotactic biopsy from 1980 to 1987 are presented. Most of them were glioblastomas (n = 43; 27%) and astrocytic tumours (n = 81; 50.9%). Twenty-nine cases of fibrillary astrocytomas (35.8% of all astrocytic tumours) showed focal anaplasia (progression). In 10 out of the 43 glioblastomas (23.3%) signs of astrocytic differentiation were clearly evident (secondary glioblastoma?). Our data confirm that neuroectodermal tumours, particularly of astrocytic series, undergo progression through anaplasia, which may be at the beginning a circumscribed phenomenon (focal anaplasia). The staging of the disease (tumour growth) into cerebral nervous system in some cases can not be correctly expressed through the neuroradiological imaging. Sometime CT scan may underestimate the true extension of the lesion. On the contrary, MR may overrate the extension of the lesion. Such mistakes in evaluation of tumour staging may be corrected through seriate stereotactic biopsy.
Between 1980 and 1987 thirty patients harbouring cerebral neuroepithelial tumours have been treated with stereotactic brachycurie therapy (18 males, 12 females), either alone (n = 16) or combined with surgery (n = 7) and/or external radiotherapy (n = 10). There were 25 slowly growing tumours (grade I n = 1; grade II n = 24). The remaining 5 were malignant tumours (grade III n = 3; grade IV n = 2). The radioactive sources utilized were 192Ir in 26 cases and 125I in 4. Twenty-eight patients underwent permanent implantation, the other two received temporary irradiation with removable after-loaded catheters. Target volume was less than 15 cm3 in 6 cases, between 16-60 cm3 in 17 and more than 60 cm3 in 7. Tumour dose at the periphery of the target volume was: 70-100 Gy in 19 and 100-130 Gy in 9 of the cases treated with permanent implantation; the patients irradiated with removable implants received 40-60 Gy in 5-7 days. General follow-up ranged between 0.3 and 6.9 years (mean = 2.5 years). The results are analyzed with reference to the following aspects: 1) natural history of the disease; 2) modalities and goal of the treatment; 3) place of brachy therapy as sole treatment and combined with the other available therapeutical means.
Tissue 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.
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Stereotactic biopsies were carried out in an attempt to define the grading of 99 neuroectodermal tumors with respect to their modalities of growth and their degree of malignancy. Valuable data has been obtained in all explored tumors. The reliability of the information provided by stereotactic biopsy depends on the careful planning of the procedure by exploring different parts of the tumor as well as of the surrounding brain tissue.
Out of 664 intracranial tumors subjected to surgical procedures since 1980, 163 underwent stereobiopsy. On the basis of this experience, we devised a scheme to help decide whether and why stereobiopsy is advisable.
15 patients with various types of surgically inaccessible epileptogenic cerebral neuroepithelial tumors were treated with stereotactic interstitial irradiation. Epilepsy was improved in all cases, being abolished in 6 and markedly reduced in another 7. The effects which became apparent soon after the radioisotope implant persisted. Possible mechanisms of the phenomenon are discussed.
The endocrinological alterations related to craniopharyngiomas are usually described as panhypopituitarism. The growth failure in the prepuberal child and/or the puberal retard are the clinical symptoms usually related to it. Nevertheless, for the peculiar diencephalic control of the prolactin (PRL) pituitary secretion, different endocrinological pictures can be observed, related to the different degree of pituitary-hypothalamic compression from the craniopharyngioma. For these reasons a dynamic PRL pre- and postoperative evaluation has been performed in 4 patients operated on for craniopharyngioma. A correlation has been made between hormonal picture, size and location of the tumor, and surgical results. The value of these data in performing an early diagnosis in children with craniopharyngioma is discussed.
Recent data from phase II trials have shown that lonidamine (LND) is effective in the treatment of tumors of various histogenesis, including gliomas. In the present work, we tested the antiproliferative effect of LND on a human glioblastoma cell line (LI) in different culture conditions. When LI are cultured in their standard conditions, a reduction of cell growth is seen after 3 days of treatment with 10(-4) M LND. It reaches 70% with respect to control after 6 days and is statistically significant. LND is ineffective at the other concentrations tested. In more stringent culture conditions, 10(-4) M LND determines a higher inhibition of cell proliferation both after 3 and 6 days of exposure, while other doses of LND are unable to affect cell growth.
Four meningiomas and six neuroepithelial tumors were assayed for the presence of estrogen receptors (ER), type II estrogen binding sites (EBS) and progesterone receptors (PgR). ER were detected in 7 out of 10 cases with levels ranging between 2.5 and 20.7 fmoles/mg of cytosolic protein. On the contrary, PgR were found in all samples (10 cases) and their levels ranged between 8.8 and 130.6 fmoles/mg of cytosolic protein. All tumor samples expressed appreciable amounts of type II EBS ranging between 452 and 2320 fmoles/mg of protein. Although the precise functional role of type II EBS is still unknown, their presence may reflect an hormonal sensitivity of these tumors.