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M Gerosa

Publications and source records attributed to M Gerosa.

At least 37 records · Page 2Linked to original sources
PubMed1996

Gamma Knife radiosurgery in skull base meningiomas. Preliminary experience with 50 cases.

Gamma Knife radiosurgery was performed on 50 patients (10 males and 40 females) with skull base meningiomas (SBMs) between February 1993 and September 1995. The patients ranged in age from 25 to 78 years (mean age 56 years). The location of the tumors was anterior fossa (n = 4), sphenoorbital (n = 2), sellar region (n = 5), cavernous sinus (n = 26), petroclival (n = 12), and occipital foramen (n = 1). The tumor volume ranged from 0.6 to 20 cm3 (mean 8.6 cm3). The mean values for dose planning were edge isodose (EI) 46.7%, edge dose (ED) 18.0 Gy, maximum dose 39.8 Gy, average dose (AD) 25.4 Gy, and average number of isocentres 5.7. The patients were analyzed for five parameters: tumor volume (< 7.5 vs. > or = 7.5 cm3); EI (< 50 vs. > or = 50%); ED (< 18 vs. > or = 18 Gy); AD (< 25 vs. > or = 25 Gy), and primary versus residual or recurrent tumors. The overall frequency of tumor growth control (TGC) was 98%, with 1- and 2-year TGC rates of 97% and 100%, respectively. The most favorable neurological results were obtained with a tumor volume < 7.5 cm3 (p < 0.05), EI > or = 50% (NS), ED > or = 18 Gy (NS) and with primary SBMs (p < 0.01). A favorable TGC was demonstrated at follow-up imaging examinations when the tumor volume was > or = 7.5 cm3 (100% TGC rate), EI < 50% (100%), ED > or = 18 Gy (100%), AD > 25 Gy (100%), in both primary SBMs (100%) and residual or recurrent SBMs (96.5%). To date, only 3 (6%) of the 50 patients have presented signs of neurological worsening related to the Gamma Knife radiosurgery. While no early complications were noted, neuroradiological follow-up did show delayed transient imaging complications (3 edema and 1 radionecrosis; 8% of all patients). In conclusion, our preliminary results seem to confirm that Gamma Knife radiosurgery is an effective and safe adjuvant or a feasible alternative primary treatment in controlling or preventing SBM progression.

Adult↗
PubMed1996

Gamma Knife radiosurgery for intracranial metastases: from local tumor control to increased survival.

We have analyzed a series of 225 patients with intracranial metastases (343 lesions), treated in our department by Gamma Knife radiosurgery over a 30-month period. We have used a modified Pittsburgh protocol and performed 242 procedures on 164 single/78 multiple lesions. Primary tumors were mostly carcinomas of the lung (52%) and breast (11.6%). Neuroradiological localization of the target was usually performed by stereotactic computed tomography. Magnetic resonance imaging was only used in special circumstances. Routine dose planning was assisted by three-dimensional reconstruction programs. Mean tumor volume was larger than expected (5.7 ml). Mean prescription dose and average dose were 21.1 and 29.9 Gy, respectively. Middle- and long-term results were evaluated in a subset of 152 patients (236 lesions) with adequate (> 4 months) follow-up. Mean follow-up was 53.1 weeks with 61/152 patients still living. There was a predominance of retrospectively classified 'not fully eligible cases' among the survivors, mainly because of uncontrolled primary tumor. The 1-year local tumor control rate was 88.2%. Treatment-related radiological (3.9%) and clinical (1.6%) sequelae were minimal. Overall mean survival in these patients (40 weeks) turned out to be higher than that commonly reported after conventional surgical-radiation treatments. It was encouraging that the mean survival of 'fully' eligible patients was 51 weeks. Karnofsky performance status and neurological (Order Grading) performance scores were consistently high for most of the follow-up period. Functional Independence and the Palliative Index were not far from the value of mean survival. The main cause of death remains uncontrolled systemic disease (64.8%). On the other hand, the relative incidence of intracranial tumor progression was considerably decreased. This indicated that these patients should perhaps be treated more aggressively and underlines the need for randomized trials to determine the optimal treatment.

Adult↗
PubMed1996

Gamma Knife stereotactic radiosurgery for uveal melanoma: clinical results after 2 years.

We report on 36 cases of uveal melanoma treated at our center between March 1993 and September 1995. There were 16 men and 20 women, aged 57 +/- 11 years. The choroid was affected in 35 patients and the ciliary-body in 1. The same preoperative and follow-up protocol was adopted for all cases. The procedure included fixation and positioning of the eye with a retrobulbar injection of long-lasting anesthetic and two extraocular muscle sutures, application of the frame, computed tomography scan localization, dose planning and treatment with the Gamma Knife. The patients were divided into three groups. Group A: 10 patients with a follow-up of 24 +/- 4 months, treated with a high dose (surface dose 58 +/- 9 Gy, maximum dose 81 +/- 15 Gy, mean dose 66 +/- 11 Gy). Group B: 9 patients with a follow-up of 16 +/- 2 months, treated with a lower dose (surface dose 41 +/- 3 Gy, maximum dose 76 +/- 10 Gy, mean dose 53 +/- 11 Gy). Group C: 17 patients with a follow-up of 6 +/- 3 months, treated with a lower dose (surface dose 42 +/- 3 Gy, maximum dose 72 +/- 16 Gy, mean dose: 54 +/- 6 Gy). In group A, we observed marked tumor regression in 9 cases, tumor recurrence in 1 case and severe complications in 5 cases (neovascular glaucoma and/or radiation retinopathy and/or radiation optic neuropathy). In group B, significant local control of the tumor was obtained with minor complications (cotton wool spots hard exudates, intraretinal hemorrhages). In group C, to date we have observed a regression of the tumor in 7 cases and 1 severe complication (neovascular glaucoma). Our data show that uveal melanomas may be adequately controlled by a high radiosurgical dosage (50-70 Gy), though there are significant side effects. Comparable levels of local tumor control may be obtainable using lower doses (40-45 Gy) which would hopefully reduce the rate of complications. However, a longer follow-up is needed for further validation of these results.

Aged↗
PubMed1995

High incidence of BK virus large-T-antigen-coding sequences in normal human tissues and tumors of different histotypes.

T-antigen (TAg) coding sequences specific for BK virus (BKV) were detected, by PCR amplification followed by Southern-blot hybridization, in a high percentage of human tumors and tumor-cell lines, as well as in normal tissues, by analysis of 189 specimens. Specifically, the BKV early region was detected in 85% of brain tumors and in all normal brain tissues, in 78% of osteosarcomas, in 38% of Ewing's tumors, in 40% of normal bone specimens and in 71% of normal peripheral blood cell samples. Wilms' tumor tissues used as a control were all negative for BKV sequences. RT-PCR analysis indicated that TAg coding sequences were expressed in specimens carrying BKV early region, ranging from 64% of the osteosarcomas to 100% of glioblastomas, Ewing's tumors, peripheral blood cells and normal bone. Moreover, DNA sequencing performed in 12 different positive samples revealed that the amplified PCR products are identical to the early-region sequence of wild-type BKV. The role of BKV TAg and its possible mechanism of action in human tumorigenesis are discussed.

Antigens, Viral, Tumor↗
PubMed1994

Risk factors for cerebral glioma in adults: a case-control study in an Italian population.

A case-control study on risk factors for cerebral tumors was conducted on an adult Italian population by the four Neurosurgical Departments of the Veneto Region, i.e. Padua, Treviso, Verona and Vicenza. The study recruited 195 cases of histologically-confirmed cerebral glioma. One hospital control was selected for each case. Cases and controls were matched for age, sex, data of hospitalization and residence. Information on both cases and controls was obtained from a relative. Uninvolved interviewers administered a structured questionnaire including items on the subject's education, occupation, lifestyle, medical history, exposure to radiation for diagnosis or therapy, head trauma and blood group and the medical history of family members. The series of cerebral tumors was first considered as an indistinct set: none of the risk factors examined showed a statistically significant association. A positive association was found with blood group A (OR = 6) when low-grade astrocytomas (n = 41) were considered separately. As for the malignant astrocytomas (n = 132), there was a suggestive but not statistically significant association with the presence of CNS tumors among first- and second-degree relatives (OR = 7.0). On the whole, this study yielded no clear and meaningful association for the various risk factors analyzed.

Adolescent↗
PubMed1989

Heterogeneity and modulation of tumor-associated antigens in human glioblastoma cell lines.

Seven human glioblastoma cell lines established in vitro from primary tumor explants were studied. A marked heterogeneity of glial fibrillary acidic protein was observed whereas vimentin was uniformly expressed by all cell lines. Indirect immunofluorescence and flow cytofluorometry revealed a heterogeneous distribution of surface GE 2 and CG 12 tumor-associated antigens (TAA's): three cell lines were positive (greater than 69% TAA-positive cells) and three cell lines were negative (less than 9% TAA-positive cells). One cell line (Hu 228) was moderately positive at early culture passages and subsequently acquired a TAA-negative phenotype. The difference in the relative amounts of surface TAA's of the three positive cell lines was less than twofold. In spite of the heterogeneous distribution of surface TAA's, all cell lines exhibited considerable amounts of intracellular TAA. Treatment with phorbol esters and density-dependent growth arrest decreased the percentage of the TAA-positive cells and the amount of cell-surface TAA's in one cell line (Hu 195). Interferon-gamma treatment in vitro increased the percentage of CG 12-positive cells by 12% and the amount of cell-surface CG 12 antigens by 38% as compared to untreated cells. The percentage of TAA-positive cells among phorbol ester-treated cells of the Hu 195 cell line was lowest 48 hours after treatment, but returned to normal values within the next 48 hours. Reduction of 3H-thymidine incorporation preceded the decrease in number of TAA-positive cells by about 18 hours. Two-color fluorescence analysis performed in positive cell lines for simultaneous determination of surface TAA's and deoxyribonucleic acid content or reactivity with the proliferation-associated Ki67 intracellular marker indicated that GE 2 and CG 12 antigens are expressed preferentially by actively proliferating glioma cells. The results of this study indicate the existence of two different phenotypes in cultured human glioblastoma cells: surface TAA-positive/cytosol TAA-positive and surface TAA-negative/cytosol TAA-positive cell populations. In addition, modulation of TAA expression was dependent on the cell-cycle differentiation stage, culture conditions, and proliferative state of the cells.

Animals↗
PubMed1988

Human recombinant interleukin-4 inhibits lymphokine-activated killer activity of sheep erythrocyte rosette-forming (E+) and -non-forming (E-) human lymphocytes.

The effect of human recombinant interleukin-4 (rIL-4) on lymphokine-activated killer activity (LAK) of peripheral blood lymphocytes (PBL) as well as sheep erythrocyte rosette-forming (E+) and -non-forming (E-) lymphocytes stimulated by human recombinant interleukin-2 (rIL-2) has been investigated. rIL-4 drastically inhibited LAK activity of PBL cultured for 18 hr and for 5 days in the presence of rIL-2. Distribution of T, B and IgG Fc-receptor-bearing lymphocytes, as assessed by immunofluorescence and flow cytometry, was no different at the end of the culture in the presence of rIL-2 plus rIL-4 than with rIL-2 alone. LAK activity of E+ and E- lymphocytes was similarly inhibited. Finally, rIL-4 did not affect the natural killer (NK) activity of rIL-2-activated PBL as assessed by the capacity of these cells to kill the appropriate NK target.

Animals↗
PubMed1988

Establishment and characterization of a new human melanoma cell line (HU 214) with a high growth potential and stable properties.

A human melanoma cell line (HU 214) with high growth potential was established from a lymph node metastasis of a patient with advanced cutaneous melanoma. The cells of this line were able to grow in monolayer (according to the Rosenblum technique) and in agar (according to the Courtenay-Mills method), and formed tumors when injected in nude mice. The line has been maintained in culture for more than 47 passages. The cell cultures were periodically characterized (every 6-8 passages) by immunohistochemistry using a panel of monoclonal antibodies (MoAbs) including MoAbs against tumor-associated antigens (antimelanoma, antiglioma and anti-LLA), against vimentin, and against major histocompatibility antigens, and including also Ki 67, a MoAb which reacts with a nuclear antigen associated with cell proliferation. The results of this characterization indicate that we have established a human melanoma cell line with a stable antigenic phenotype during subculturing, poorly differentiated cells, and a high growth potential.

Animals↗
PubMed1988

Human glioma cell lines: tumour associated antigens distribution and sensitivity to antibody-toxin or ligand-toxin conjugates. A preliminary report.

We have investigated the phenotype of seven human glioma cell lines established in vitro from primary tumour explants. Indirect immunofluorescence and flow cytofluorimetry revealed a heterogeneous distribution of surface GE 2 and CG 12 Tumour Associated Antigens (TAA). In one group of cell lines TAA were detected both at the cell surface and in the cytosol, whereas in a second group of glioma cell lines TAA were found only in the cytosol. We have also investigated the sensitivity of glioma-derived cell lines to antibody-toxin and ligand-toxin conjugates (Immunotoxins). Monoclonal antibodies anti GE 2 antigen linked to ricin toxin A subunit (RTA) showed poor cytotoxicity, which increased about 50 fold when the whole toxin was linked to anti GE 2 monoclonals. Treatment with human recombinant interferon gamma (IFN-gamma) greatly augmented the percentage of HLA-DR+ cells and the amount of HLA-DR antigens per cell. IFN-gamma treatment resulted in a net increase of sensitivity to anti HLA-DR Immunotoxins (IT). Human diferric transferrin linked to RTA exhibited a potent cytotoxic effect against human glioma-derived cells when used in the presence of the lysosomotropic carboxylic ionophore monensin.

Antibodies, Monoclonal↗
PubMed1988

Spontaneous spinal haematomas.

A series of 10 surgically treated "spontaneous" spinal haematomas (7 cases with epidural, 3 with intramedullary location), is presented. Symptomatology was rarely acute. Clinical onset was mostly dominated by spinal or radicular pain, followed by severe motor deficit. Surgical outcome was satisfactory in the majority of cases. Age, duration of symptoms, haematoma site and size appeared to have no influence on final outcome. This was significantly correlated only with the preoperative neurological condition.

Adult↗
PubMed1985

Investigation of resistance to DNA cross-linking agents in 9L cell lines with different sensitivities to chloroethylnitrosoureas.

The 9L-2, 9L-7, and 9L-8 cell lines, derived from the 9L in vivo rat brain tumor, were treated with nitrosoureas that can alkylate and cross-link DNA and carbamoylate intracellular molecules to various extents. Compared to 9L cells, 9L-2 cells were very resistant to the cytotoxic effects of 1,3-bis(2-chloroethyl)-1-nitrosourea, and to 2-[3-(2-chloroethyl)-3-nitrosoureido]-D-deoxyglucopyranose. The sensitivity of 9L-7 and 9L-8 cell lines to these drugs was intermediate between 9L and 9L-2. Treatment of 9L, 9L-2, 9L-7, and 9L-8 cell lines with 1,3-bis(trans-4-hydroxycyclohexyl)-1-nitrosourea produced approximately the same level of cell kill. Compared to 9L cells, 9L-2 cells are 10-fold more resistant to the cytotoxic effects, 34-fold more resistant to the induction of sister chromatid exchanges, and have 40% fewer DNA interstrand cross-links caused by treatment with 3-(4-amino-2-methyl-5-pyrimidinyl)methyl-1-(2-chloroethyl)-1-nitrosourea . In contrast, treatment of 9L and 9L-2 cells with 1-ethylnitrosourea produced approximately the same level of cell kill and induction of sister chromatid exchanges. Our results suggest that the resistance of 9L-2, 9L-7, and 9L-8 cells is related to DNA cross-linking and not to alkylation or carbamoylation. We studied the effects of other agents that form DNA cross-links with structures different from those formed by treatment with chloroethylnitrosoureas (CENUs) in 9L and 9L-2 cells. In contrast to results obtained with CENUs, 9L-2 cells were 2-fold more sensitive to the cytotoxic effects, 2-fold more sensitive to the induction of sister chromatid exchanges, and had 3-fold more cross-links formed than 9L cells treated with nitrogen mustard. However, the amount of cell kill, number of sister chromatid exchanges induced, and the DNA cross-linking were the same for 9L and 9L-2 cells treated with cis-diamminedichlorplatinum(II). Our results indicate that cellular resistance to CENUs is highly specific and that the mechanism of resistance does not allow cross-resistance with other DNA cross-linking agents. These and other results suggest that when DNA repair processes mediate cellular resistance to CENUs, other cross-linking agents will not be cross-resistant unless they form alkylation products that are affected by repair processes that mediate resistance to CENUs.

Animals↗
PubMed1982

Age-related chemosensitivity of stem cells from human malignant brain tumours.

After radiation therapy and chemotherapy for malignant glioma, patients aged 50 or under survive longer than patients over 50. Data from Brain Tumor Study Group trials show that, without treatment, these age groups have similar survival; therefore unperturbed tumour growth does not account for the difference. Sixteen consecutive patients with malignant glioma were studied, half of whom were less than or equal to 50 years of age; none had been treated before initial surgery, and all were subsequently treated with radiation and chemotherapeutic agents (in all but two patients, with nitrosoureas). Median survival of those aged greater than 50 was less than or equal to 50 years was 54 + weeks whereas that of those aged greater than 50 was 37 weeks. The longer survival for younger patients could not be attributed to tumour type, size, or location, pretreatment Karnofsky status, or mode of treatment. In-vitro sensitivity testing of clonogenic cells obtained from biopsy specimens showed that tumour cells from seven of eight patients aged less than or equal to 50 years were sensitive to 1,3-bis (2-chloroethyl)-1-nitrosourea (greater than 40% cell kill at clinically achievable concentrations) compared with only one patient with sensitive cells out of eight older patients. Patient age was inversely correlated with in-vitro cell kill, and patients with sensitive cells were significantly younger than those with resistant cells. Therefore influence of age on survival after treatment of malignant gliomas is probably due to inherent differences in the sensitivity of clonogenic cells to radiation and/or chemotherapeutic agents.

Age Factors↗
PubMed1981

Posttraumatic intraventricular haemorrhages.

Of a series of 350 patients studied for blunt head trauma by CT scan 10 were found to have an intraventricular haemorrhage (IVH); in 8 cases we could find concomitant CT abnormalities as well as intracerebral contusion or haemorrhage, and in two cases no other CT abnormality was noted. CT scan represents the first reliable and non-surgical tool for identifying this process. Two possible mechanisms that govern the formation of an IVH are postulated: a) an erosion of the ventricular wall by an intracerebral haemorrhage; b) the rupture of subependymal veins deformed by the negative pressure following dilatation of the ventricular wall. The prognosis in our cases is severe.

Adolescent↗
PubMed1981

Long-term immunological investigation of malignant intracranial gliomas.

In this study, 118 consecutive adult patients with supratentorial gliomas underwent preoperative immunological monitoring, with particular regard to B-lymphocyte and T-lymphocyte markers. Most patients were treated surgically and with radiotherapy. Three months later, they were readmitted for postoperative immunological investigation and follow-up control. A total of 76 cases could thus be completely investigated and were statistically eligible for evaluation. A pronounced failure of T-cell-mediated immunity was observed: "E-active" rosette-forming cells and mitogen-induced blastogenesis tests turned out to be markedly depressed, with a slight postoperative recovery. Spontaneous cell-mediated cytotoxicity was significantly (p less than 0.01) increased both in preoperative and postoperative findings. The main immunodiagnostic patterns (immunoglobulins assay, surface immunoglobulins, "mouse" rosettes) concerning the B-cell-dependent "pool" were found to be within normal limits.

Adult↗
PubMed1981

Gliomas of the optic nerve and chiasm. A clinical review.

A series of 24 children with anterior optic gliomas, observed and for the most part operated upon in a neurosurgical service, is reviewed. A low incidence of unilateral nerve tumors and of associated neurofibromatosis, and a rather high frequency of precocious or pseudoprecocious puberty were noted in comparison with other series. Most tumors were low-grade growths. The results of surgical treatment reflect a good prognosis for unilateral tumors and an increasing prognostic ominousness for the posterior neoplastic development. Cerebrospinal fluid shunts and radiation treatment do have a role as adjuncts to surgical exploration and biopsy, which are generally indicated since no preoperative test seems to grant an absolute diagnosis. The opinion that chiasmal tumors should not be treated at all is not shared. When the treatment of an illness falls as far short of the ultimate, as does the therapy of neoplastic disease, then it is necessary to reconsider frequently the principles upon which it is based and the results it achieves. These results are two-fold, curative and palliative and, while our efforts are directed toward the former, we realize only too frequently that the best results will sometimes lie in palliation. The disappointment in accepting this lesser goal must not allow us to underestimate its importance or neglect the help it may give.

Adolescent↗