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Biomedical subjects

A Silvani

Publications and source records attributed to A Silvani.

At least 37 records · Page 2Linked to original sources
PubMed2001

Fotemustine combined with procarbazine in recurrent malignant gliomas: a phase I study with evaluation of lymphocyte 06-alkylguanine-DNA alkyltransferase activity.

The aims of this phase I study in patients with recurrent malignant gliomas were to determine the maximum tolerated dose (MTD) and toxicity profile of fotemustine when combined with a fixed dose of procarbazine (PCZ), and to evaluate the extent of O6-alkylguanine-DNA alkyltransferase (ATase) depletion in circulating lymphocytes during treatment. Sixteen patients received an induction cycle consisting of 100 mg/day oral PCZ for 12 consecutive days and a 1-h intravenous infusion of fotemustine given 4 h after PCZ on days 5 and 12 at escalated doses (50, 75, 100 and 125 mg/m2/day). After a 6-week rest period, a maximum of 4 maintenance cycles (PCZ 300 mg/day, 4 days; fotemustine, day 4) was given every 4 weeks. ATase activity was measured on days 1, 5 and 12 over 4 h after PCZ intake. Fifteen patients had previously received at least one nitrosourea-based chemotherapy, associated with PCZ in 12 cases. The MTD of fotemustine was 125 mg/m2 (days 5 and 12) with myelosuppression as the dose limiting toxicity (DLT). At this dose level, half of patients experienced grade 3 anemia, neutropenia or thrombopenia. No extra-hematological DLT was observed. No significant depletion of ATase activity by PCZ was evidenced. One partial response and 7 stable diseases were obtained leading to a disease control rate of 50%. The median times to progression and survival were 2.6 and 9.7 months, respectively. This combined regimen of PCZ and fotemustine was well tolerated with a good disease control rate in heavily pretreated glioma patients and merits further investigation in phase II studies.

Adult↗
PubMed2001

Efficacy of intratumoral delivery of mitoxantrone in recurrent malignant glial tumours.

Ninety-nine patients bearing recurrent malignant glioma sequentially selected according to strict eligibility criteria (72 GBL and 27 AA) entered the study. All patients were previously managed with radiotherapy 60 Gy total dose and chemotherapy with nitrosoureas and platinum compounds. At recurrence they were subdivided in homogeneous groups, all treated with the same systemic chemotherapy protocol: 27 GBL (group A) only systemically treated, 20 GBL (group B) treated also locally by delivering 4mg of mitoxantrone every 20 days through the Ommaya reservoire, and 25 GBL (group C) treated with a second surgery and locally as group B. Of the AA group, 13/27 were treated locally trough the Ommaya reservoir after repeat surgery. A trend to different demographic features among subgroups (with locoregionally treated patients and patients undergoing repeat surgery being younger than the others) was seen in this non-randomized study, but this was not statistically significant. Median overall survival was 27, 26 and 15.5 months respectively for groups c, b and a (log-rank = 0.1). After tumor recurrence median survival was 16.8, 12 and 6.6 months respectively for groups c, b and a (log-rank = 0.001) For the 29 AA, overall survival was 48.5 and 100 months (log-rank = 0.03) if treated locally with second tumor debulking. Our results stress the opinion that a second operation could be indicated only if it is a part of a therapeutic protocol to allow a locoregional treatment. Moreover we can finally assume that local delivery of chemotherapy after tumor recurrence, possibly extends patients survival but certainly improves the number of long-survivors.

Adolescent↗
PubMed2000

Embryonal tumors in the adult population: implications in therapeutic planning.

The natural history of neuroectodermal tumors is still debated as far as prognostic factors are concerned; the same uncertainty applies to the optimal radiotherapy schedule and even more to the presumptive additive effect of chemotherapy. The rarity of these tumors and the heterogeneity of management make interpretation of literature data also more difficult. We evaluated clinical course in a cohort of 39 patients, including 31 with medulloblastoma (MB) and 8 with primitive neuroectodermal tumors (PNET). All patients were treated with radiotherapy, a standardized chemotherapy protocol including PCV scheme, and a second-line chemotherapy with cisplatin and etoposide (VP16) at recurrence. In 27 patients, intrathecal chemotherapy was also delivered. Median follow-up was 10.8 years. Overall, PNET had a worse outcome as compared to MB: median survival times were 42.8 vs. 92.6 months, respectively (p = 0.05). At 5 years, 45% of MB patients are alive. No significant difference in disease-free period was found between patients of different age, desmoplastic variant, tumor localization, or extent of surgery. Patients considered to be "high risk" had a significantly shorter disease-free period as compared with low-risk patients (27 vs. 54.7 months, p = 0.04). Systemic or intrathecal chemotherapy did not influence progression-free survival (PFS). However, in the majority of chemotherapy-treated patients, a low-dose craniospinal radiotherapy was also delivered. This combination of treatments may have avoided the expected increased percentage of failure. Moreover, more than half of recurrent patients had a partial response to chemotherapy that extended survival for approximately 3 years. Repeated surgery and chemotherapy at recurrence favorably influenced survival time.

Adult↗
PubMed2000

Cisplatin and BCNU chemotherapy for anaplastic oligoastrocytomas.

In this study 32 newly diagnosed anaplastic oligoastrocytoma patients were enrolled (median age of 41 years, range 19-63; median Karnofsky performance status of 90, range 70-100). All patients were treated with Cisplatin (109 mg/m2) and BCNU (160 mg/m2). The chemotherapy started in the first week after surgery and it was administered every 6 weeks (5 scheduled cycles) for a total of 127 cycles. After the second cycle of chemotherapy all patients received radiotherapy (56.5 Gy). The median follow-up was 63.2 months (10-91). Nine patients were reoperated-on. The median time to tumor progression (TTP) and median survival time (ST) for the whole group of patients were 54.6 and 70.1 months, respectively. A proportional hazard model was used to look at potential prognostic factors for survival including lower age (< 40 years), extent of surgery (total/subtotal versus partial) and reoperation. When we analyzed the group of patients with total/subtotal surgery or age under 40 years the median ST could not be assessed due to the high number of surviving patients after a follow-up of 52 months. The median ST for the older patients or for patients partially operated-on was 54.1 and 42.2 months. In our study only total/subtotal surgery predicted for longer survival (p < 0.001). This schedule of treatment provides durable response in a selected group of anaplastic oligoastrocytoma patients.

Adult↗
PubMed2000

The photochemical behavior of colchicone and thiocolchicone.

The irradiation of colchicone 5 led to the formation of lumicolchicone 7. The same reaction cannot be obtained by using thiocolchicone 6 as substrate. Transient absorption spectroscopy of colchicone and beta-lumicolchicone showed that probably the photoisomerization occurred on colchicone in its first excited singlet state. The spectroscopic data are in agreement with the hypothesis that lumicolchicone was generated in the ground state from the S1 state of colchicone without the presence of any intermediate. Semiempirical calculations on colchicone and thiocolchicone showed that the highest single occupied molecular orbital and the lowest unoccupied molecular orbital of the singlet excited colchicone can give a disrotatory ring closure to 7, while thiocolchicone cannot give the same type of process.

Colchicine↗
PubMed1999

Circulating intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and plasma thrombomodulin levels in glioblastoma patients.

Cellular adhesion molecules have been implicated in tumor progression and metastasis. Serum samples from 22 patients with glioblastoma (GBM), before surgery, and 19 sex and age matched healthy controls were analyzed for circulating levels of ICAM-1 and VCAM-1. At the same time also soluble plasma thrombomodulin, a marker of endothelial cell damage and activation, was detected. Soluble ICAM-1 and VCAM-1 levels were comparable in glioblastoma patients and healthy controls, while plasma thrombomodulin (TM) was significantly increased in cancer patients. There was no correlation between thrombomodulin levels and the presence of an intratumoral hemorrhage detected by CT scan, while entity of post-contrast enhacemement at CT correlated with higher TM levels. Further study with serial sampling of GBM patients and correlation with enhancement at CT will allow to ascertain the value of serum TM as a marker of disease recurrence or angiogenesis in those tumors.

Female↗
PubMed1999

Distribution of daunorubicin and daunorubicinol in human glioma tumors after administration of liposomal daunorubicin.

DaunoXome is a liposome formulation containing daunorubicin (DM). Encapsulation of the drug in liposomes presents the advantage of low-level systemic exposure and better drug penetration into the tumor. We studied the distribution of DM and its 13-dihydro metabolite, daunorubicinol (DMol), in surgical biopsies from different parts of glioblastomas. The study was performed in eight patients with recurrent glioblastoma, all of whom had previously undergone surgery and been treated with radiotherapy and chemotherapy, who received 50 mg of DaunoXome as a 1-h infusion. Surgery was performed at 24 and 48 h after the infusion in seven cases and one case, respectively. Biopsies were divided into three parts: the central area of the tumor, peripheral tumor tissue, and brain-adjacent tumor (BAT) tissue. A complete plasma pharmacokinetics study was conducted in seven cases, with samples being taken for up to 48 h after the end of the infusion. DM and DMol were determined in plasma and tissue by high-performance liquid chromatography with fluorescence detection after solvent extraction. At 24 h, concentrations of DM and DMol in the central part of the tumor ranged between < 0.005 and 0.80 microg/g and between 0.005 and 1.58 microg/g, respectively. Concentrations were similar in the peripheral tumor and in BAT tissue. From the data obtained on the patient who underwent surgery at 48 h it appears that DM and DMol remain in tumor tissue for a long time, the concentrations being 0.4 and 2.8 microg/g, respectively. DaunoXome was rapidly cleared from the body, with the plasma levels of DM and DMol determined at 48 h lying in the range of < 5-50 and < 5-20 ng/ml, respectively. The mean (+/-SD) half-life and plasmatic clearance of DM were 4.8+/-1.0 h and 0.2+/-0.06 l h(-1) m(-2). In conclusion, DaunoXome achieved and maintained potentially cytotoxic levels of both DM and DMol in glioblastoma for a long time in association with low-level systemic exposure. Further studies are therefore warranted. Although only preliminary and obtained in previously treated patients, these data suggest that DaunoXome merits investigation in CNS tumors.

Adult↗
PubMed1999

Chemotherapy is effective as early treatment for primary central nervous system lymphoma.

Primary central nervous system lymphoma (PCNSL) is a lymphoma arising within the brain or spinal cord in the absence of evident localisation outside the central nervous system (CNS). Poor results in the management of relapsed PCNSL justify the need for vigorous initial therapeutic regimens, and chemotherapy should not be reserved for recurrent disease. Chemotherapy (MBACOD scheme) was delivered prior to irradiation in a group of 20 PCNSL patients, another 8 PCNSL patients underwent radiotherapy only, and the overall survival was evaluated. Computed tomography (CT) images in the group of patients treated with chemotherapy, showed there to be 70% complete responders (CR), 15% non-responders (NR) and 15% partial responders (PR). Half of the CR were scheduled for radiotherapy only at tumour recurrence. The median disease-free period and survival time of the whole group treated with early chemotherapy followed by radiotherapy were 24 and 32 months, respectively, but in the subgroup of CR (70%), taking into account also the patients not yet receiving radiotherapy, these were 38 and 48 months, respectively. The disease-free and survival times in the group of CR (75%) of patients treated with radiotherapy only were 13 and 18 months, respectively. At tumour recurrence, CR to chemotherapy had a second disease-free period longer than 2 years after radiotherapy. Our data support the belief that in scheduling the treatment of PCNSL after histological diagnosis, the first step is to devise high-dose chemotherapy with drugs able to cross an intact blood-brain barrier. The results of our primary approach with early chemotherapy in PCNSL support a consensus to continue chemotherapy until tumour recurrence, and only at that event to initiate radiotherapy. It is a challenge and an option worthy of continuing investigation.

Adrenal Cortex Hormones↗
PubMed1999

Locally delivered chemotherapy and repeated surgery can improve survival in glioblastoma patients.

We treated 54 patients, newly diagnosed for glioblastoma, with systemic chemotherapy (carmustine (BCNU) 100 mg/m2 and cisplatin 90 mg/m2 every 6 weeks) and radiotherapy soon after surgery. In 10 cases the treatment was combined with locoregional chemotherapy (1 mg bleomycin on days 1-2, and 3 mg mitoxantrone on day 3, repeated every 20 days) administered from an Ommaya reservoir. At tumor recurrence, all patients were treated with procarbazine, lomustine and vincristine (PCV); 15 of 54 were reoperated and treated with locoregional chemotherapy. The median time to disease progression (TTP) and overall survival time (ST) for the whole group were 10.8 and 23.1 months, respectively. The ST of the 15 reoperated patients who also received locoregional treatment at disease recurrence was 27.6 months; this was significantly longer than that of patients not reoperated and not treated locally (log-rank p=0.04). The results in our reoperated subgroup support the opinion that a second operation could be suitable if it is part of the whole program of treatment.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1999

Tumor necrosis factor microsatellite polymorphisms in Italian glioblastoma patients.

Tumor necrosis factor (TNF) genes map on the short arm of chromosome 6 and have been described to contain several polymorphic regions, the most informative of which are TNFa (13 alleles) and TNFb (8 alleles) microsatellites. We analyze TNFa and TNFb microsatellite polymorphisms in 58 Italian patients with glioblastoma (GBL) and 95 unrelated healthy controls. At the TNFb locus, we detected a statistically significant decrease in the TNFb4 allele in GBL patients compared with the controls (P = 0.002; Pcorr = 0.015). Among the patients, 8 were homozygous TNFb4 (+/+), 23 were TNFb4 heterozygous (+/-), and 27 were negative for TNFb4 (-/-). In a comparison with the controls, we detected a statistically significant difference (P = 0.017). In fact, although no difference was detected in +/-, statistically significant differences were detected both for an increase in -/- and for a decrease in +/+ in the patient groups (P = 0.006 and P = 0.047, respectively). These data suggest that TNFb4-negative individuals might preferentially develop a Th2-type immune response that could lead to a reduction in antitumor activity.

Adolescent↗
PubMed1999

Interstitial chemotherapy plus systemic chemotherapy for glioblastoma patients: improved survival in sequential studies.

We investigated the efficacy of 3 different systemic chemotherapy regimes in 122 patients with histologically confirmed glioblastoma, KPS > 60, age < 65. Locoregional chemotherapy was delivered to 22 patients from all three systemic chemotherapy groups. Chemotherapy was given before and during radiotherapy, which was the same for all patients consisting of unconventional fractionation with a break between courses. Survival (Kaplan-Meier) was significantly longer in the subgroup receiving cisplatinum plus BCNU compared to those receiving cisplatinum plus etoposide or carboplatinum plus BCNU with median survival time 21.5 months, 15 months and 15 months respectively (log rank test p = 0.01). Survival was also significantly longer in patients who received locoregional therapy compared to those who received only systemic chemotherapy (21 vs 15 months, p = 0.01). Univariate analysis showed that age, postoperative Karnofsky status and extent of resection were not predictive of survival in the series, although there were trends to better outcome in younger patients and those undergoing total/subtotal resection. Age, systemic chemotherapy type and interstitial treatment were included in a multivariate analysis, and both locoregional treatment and chemotherapy with cisplatinum plus BCNU were significantly predictive of survival [P = 0.01]. These encouraging preliminary results suggest that further trials with locoregional and systemic therapy prior to radiotherapy are worth pursuing.

Adult↗
PubMed1998

Transduction of the SkBr3 breast carcinoma cell line with the HOXB7 gene induces bFGF expression, increases cell proliferation and reduces growth factor dependence.

Several melanomas, carcinomas, glioblastomas and leukemias showed coordinated expression of HOXB7 and bFGF with exception of the SkBr3 mammary carcinoma that was negative for both. Transduction of HOXB7 gene into SkBr3 cells, induced bFGF expression, increased growth rate, independence from serum withdrawal and ability to form colonies in semisolid medium. ELISA assay showed that most of bFGF was associated to cell lysate when cells were cultured at 1% serum whereas in cells kept to 10% serum bFGF was detected both within cell lysate or secreted into cell supernatants. Antisense oligos to bFGF inhibited the growth of cells cultured in 1%, indicating that beside the possible activation of additional genes other than bFGF by HOXB7 transduction, only bFGF induction accounts for the observed results. Moreover, since inhibition of cell proliferation occurred in cells kept in 1% but not 10% serum, a bFGF intracrine loop appears operative in serum starved SkBr3/HOXB7 cells. Also, these results further indicate bFGF as target of HOXB7.

Agar↗
PubMed1998

[MALT lymphoma of the left lacrimal and mammary glands, liver cirrhosis caused by HCV and type II cryoglobulinemia].

We describe a case of MALT (mucosa-associated lymphoid tissue) lymphoma associated to post-hepatitis C liver cirrhosis, type II cryoglobulinaemia, gastrointestinal bleedings and thromboses. HCV infection justified the association between the first three pathologies, while gastrointestinal bleedings and thromboses were respectively attributed to portal hypertension secondary to liver cirrhosis and to some thrombophilic conditions. Among the latter there was also an antithrombin III deficiency. The singularity of the case and some difficulties met in its treatment, justify the report.

Aged↗
PubMed1997

Primary cerebral non-Hodgkin's lymphoma (PCNSL): a review of new trends in management.

Primary central nervous system lymphoma (PCNSL) is a rare tumor but it is rising in incidence in both AIDS and non AIDS populations. It is a non-Hodgkin's lymphoma that usually presents itself as a brain tumor, but leptomeninges, eyes and also spinal cord are frequently affected. The management of PCNSL patients has evolved in the last years. The role of surgery has been restricted for diagnosis only because the exeresis of the tumor is ineffective owing to its multifocal and infiltrative nature. Therefore, stereotactic biopsy is the way of choice for documenting the diagnosis. The standard treatment was radiotherapy started after diagnosis and followed by chemotherapy at recurrence. PCNSL is radiosensitive and chemosensitive: about 70% of patients respond to one or other of these treatment modalities but usually PCNSL recurs locally after radiotherapy. More recently the inclusion of high doses ARA-C and Methotrexate delivered prior radiotherapy have shown significant high responses and prolonged survivals.

Brain Neoplasms↗