Cognitive awareness after treatment for high-grade glioma.

Objective: In patients with brain lesion, awareness of cognitive deficits is an important aspect of disease awareness. Glioblastoma (GBM) and anaplastic astrocytoma (AA) can cause cognitive deficits, but, to date, awareness of these deficits has not been documented. This study aimed to test cognitive awareness in these patients after the end of treatment.

Quality of life and brain tumors: what beyond the clinical burden?

This study analyzed the subjective facets of quality of life (QoL) and their relation to the type of brain tumor (BT) and phase of disease. Two hundred and ninety-one patients with pinealoblastoma, medulloblastoma, low-grade glioma, anaplastic astrocytoma, or glioblastoma were evaluated. With respect to 110 healthy controls, patients in the phases of radiotherapy/chemotherapy, stable disease, or tumor recurrence were significantly more anxious and depressed compared with patients in the early postoperative period.

Cisplatinum and BCNU chemotherapy in primary glioblastoma patients.

Background: The prognosis of patients with glioblastoma is very poor with a mean survival of 10-12 months. Currently available treatment options are multimodal, which include surgery, radiotherapy, and chemotherapy. However, these have been shown to improve survival only marginally in glioblastoma multiforme (GBM) patients.

Treatment of recurrent glioblastoma: can local delivery of mitoxantrone improve survival?

In this study, the records of 276 adult patients with recurrent glioblastoma (GBM) treated at recurrence at our institution between 2004 and 2006 were reviewed for progression-free survival (PFS), overall survival (OS), and toxicity. At recurrence, all patients underwent systemic treatment with temozolomide (200 mg/sqm on days 1-5 every 28 days) until tumor progression. Patients, whose tumor was judged resectable without risk of adjunctive neurological deficit, underwent a second surgery with or without positioning of a Rickam/Ommaya reservoir.

Valproic acid increases the in vitro effects of nitrosureas on human glioma cell lines.

Valproic acid (VPA) has been recently investigated for its anticancer properties in different tumors, including malignant gliomas. The aim of the present work was to evaluate the effects of VPA, alone or in combination with other chemotherapeutic drugs, on in vitro growth of human glioma cell lines. A172, U373, U138, U87, and SW1783 were treated with VPA alone or in combination with mitoxantrone, etoposide, or 1,3-bis(2-chloroethyl)-l-nitrosourea (BCNU).

Prognostic factors for survival in 676 consecutive patients with newly diagnosed primary glioblastoma.

Reliable data on large cohorts of patients with glioblastoma are needed because such studies differ importantly from trials that have a strong bias toward the recruitment of younger patients with a higher performance status. We analyzed the outcome of 676 patients with histologically confirmed newly diagnosed glioblastoma who were treated consecutively at a single institution over a 7-year period (1997-2003) with follow-up to April 30, 2006. Survival probabilities were 57% at 1 year, 16% at 2 years, and 7% at 3 years.

Salvage chemotherapy with procarbazine and fotemustine combination in the treatment of temozolomide treated recurrent glioblastoma patients.

The purpose of this study was to evaluate safety and efficacy of Procarbazine (PCB) and fotemustine (FTM) combination in the treatment of pre-temozolomide treated, recurrent GBM patients. The primary end-point was progression free survival at 6 months (PFS-6). Secondary end-points were overall survival, response rates (CR + PR) and toxicity.

Methylation of O6-methylguanine DNA methyltransferase and loss of heterozygosity on 19q and/or 17p are overlapping features of secondary glioblastomas with prolonged survival.

Purpose: Recent data suggest that methylation of the DNA repair gene O(6)-methylguanine DNA methyltransferase (MGMT), by increasing the chemosensitivity of glioblastoma multiforme, is significantly associated with improved prognosis. Results in contradiction with these findings, however, are present in the literature and the clinical and genetic context framing MGMT methylation is poorly characterized.

Experimental Design: To address these issues, we have investigated the MGMT methylation status, clinical and magnetic resonance imaging characteristics, and relevant genetic features (loss of heterozygosity on 17p and 19q, EGFR amplification, and p53 mutations) in a retrospective study on 86 patients affected by glioblastoma multiforme: 72 patients had a clinical history indicating de novo insurgence of the tumor and the remaining 14 were secondary glioblastoma multiforme.

In vitro study of low molecular weight heparin effect on cell growth and cell invasion in primary cell cultures of high-grade gliomas.

Heparins represent the first choice for prevention and treatment of venous thromboembolism. In particular, low molecular weight heparins (LMWHs) provide pharmacokinetic advantages compared to unfractionated heparin (UFH): longer half-life, better bioavailability, and lower binding to plasma proteins. In the last years results of preclinical and clinical studies have suggested that LMWH may be able to inhibit cell growth, cell invasion, and angiogenesis, which are key mechanisms involved in tumor progression, possibly influencing favorable clinical outcome in at least a proportion of cancer patients.

Glioblastoma-derived tumorospheres identify a population of tumor stem-like cells with angiogenic potential and enhanced multidrug resistance phenotype.

We investigated in vitro the properties of selected populations of cancer stem-like cells defined as tumorospheres that were obtained from human glioblastoma. We also assessed their potential and capability of differentiating into mature cells of the central nervous system. In vivo, their tumorigenicity was confirmed after transplantation into the brain of non-obese diabetic/severe combined immunodeficient (NOD-SCID) mice.

Surgifoam and mitoxantrone in the glioblastoma multiforme postresection cavity: the first step of locoregional chemotherapy through an ad hoc-placed catheter: technical note.

Objective: To investigate the safety and feasibility of a novel form of treatment offered by the direct intraoperative application of a Surgifoam-mitoxantrone mix into a glioblastoma multiforme postresection cavity. A technique for the placement of an intracavity catheter connected with a subcutaneous reservoir for further locoregional mitoxantrone administration is also described.

Methods: Between January and December 2004, 22 consecutive recurrent glioblastoma multiforme patients (14 men, 8 women; age, 56-72 yr; average, 64 yr; median, 65 yr) were enrolled in this study.

Prognostic value of CXCL12 expression in 40 low-grade oligodendrogliomas and oligoastrocytomas.

Both clinical and biological features have been reported as prognostic factors in low-grade gliomas. Among these, histotype, tumor size, enhancement, age and genetic pattern. Microvessel density (MVD) has been correlated to clinical outcome in astrocytomas, but its impact in oligodendrogliomas and mixed tumors is not sure.

Reclassification of oligoastrocytomas by loss of heterozygosity studies.

Oligoastrocytomas (OAs) are WHO grade II or III tumors composed of a mixture of 2 neoplastic cell types morphologically resembling the cells in oligodendrogliomas and diffuse astrocytomas. Investigations on the genetic profile of OAs may yield important information for their classification and help for their clinical management. We have studied, in 94 OAs (46 WHO grade II and 48 WHO grade III), the patterns of loss of heterozygosity (LOH) of 4 genomic regions: 1p, 19q, 17p and 10q.

Production and post-surgical modification of VEGF, tPA and PAI-1 in patients with glioma.

Malignant gliomas are associated with risk of thromboembolism, but the molecular link between tumor and peripheral pro-coagulant status has not been elucidated. Vascular Endothelial Growth Factor (VEGF), tissue-type Plasminogen Activator (tPA), Plasminogen Activator Inhibitor-1 (PAI-1) and lipoprotein (lp) (a) influence the pro-coagulant status. To assess whether the presence of the tumor influenced the peripheral levels of VEGF, tPA, PAI-1 and lp(a), we studied the expression and secretion of VEGF, tPA, PAI-1 and lp(a) in glioma specimens, in peripheral blood and in primary glioma-derived cultures.

Instability of mitochondrial DNA and MRI and clinical correlations in malignant gliomas.

Mutations and instability of mitochondrial DNA (mtDNA) are frequent in tumors but their pathogenic relevance is not established. To assess their role in the clinical management of malignant gliomas we have studied the D loop of mtDNA in 42 such tumors. Alterations were found in 36% of the cases.

Intratumoral delivery of mitoxantrone in association with 90-Y radioimmunotherapy (RIT) in recurrent glioblastoma.

Twenty-six recurrent Glioblastoma (rGBM) patients sequentially treated at the National Neurological Institute 'C Besta' were enrolled for a second surgery in order to remove recurrent tumor and to place an Ommaya reservoire to allow local delivery of chemotherapy and local pre-targeted radio-immunotherapy (RIT). All patients had partial tumor resection and 75% of them had a residual tumor mass after exeresis larger than 2 cm. After surgery all patients were managed with a second line systemic chemotherapy (PCV).

Combined chemotherapy and radiotherapy for intracranial germinomas in adult patients: a single-institution study.

We report on our experience in the treatment of intracranial germinomas (18 pure germinomas and two germinomas with syncytiotrophoblastic giant cells) according to a strategy of radiotherapy doses and fields reduction after a neoadjuvant chemotherapy (Cisplatin-vinblastine and bleomycin combination). Radiation therapy was delivered after the completion of the third and last course of chemotherapy. For the solitary germinoma the target volume was the gross tumour volume.

In vitro effects of topotecan and ionizing radiation on TRAIL/Apo2L-mediated apoptosis in malignant glioma.

The survival of patients with malignant gliomas is still unsatisfactory despite multimodality treatment, therefore new therapeutic strategies are required. Tumor necrosis factor apoptosis related ligand (TRAIL/Apo2L), a member of the tumor necrosis factor superfamily, may induce apoptotic cell death in several tumors, but not in normal cells, upon binding with specific receptors. In the present study, the expression and function of TRAIL receptors (TRAIL-R1/DR4 and TRAIL-R2/DR5) has been investigated in five human glioma cell lines (U87, U138, U373, A172, SW1783) in ex vivo tumors and in primary cultures obtained from the tumors.

Effect of association of temozolomide with other chemotherapic agents on cell growth inhibition in glioma cell lines.

Despite progresses in surgery and treatments of malignant gliomas, prognosis of these tumors remains poor, with a median life expectancy of 12 months in glioblastomas. Chemotherapy (mostly with nitrosoureas) has been demonstrated to prolong overall survival, but the entity of this improvement is slight and disease recurrence/progression is the rule, stressing the need for multimodality treatment. In this work we investigated the effect of association of temozolomide (TMZ), an orally bioavailable alkylating agent, with three chemotherapeutic drugs, liposomal doxorubicin (DOXO), cis-platinum (CDDP).

CXCL12 in malignant glial tumors: a possible role in angiogenesis and cross-talk between endothelial and tumoral cells.

CXCL12 (stromal cell-derived factor-1/CXCL12) regulates leukocyte, endothelial and hematopoietic precursor migration, bone-marrow myelopoiesis and angiogenesis. CXCL12 and its receptor CXCR4 are over-expressed in malignant gliomas, which are highly vascularized tumors with a poor prognosis. We studied the expression of CXCL12 and CXCR4 in glioma cell lines, endothelial cells, tissue sections and endocavitary fluids from patients with gliomas.

Phase II trial of cisplatin plus temozolomide, in recurrent and progressive malignant glioma patients.

We report a phase II trial of cisplatinum and temozolomide (TMZ) combination in recurrent malignant glioma patients. The DNA repair protein O(6)-alkylguanine-DNA alkyltransferase (AGAT) is important in glioblastoma resistance to alkylating antitumor agents. In vitro, cisplatin (CDDP) decreases MGMT activity in a time- and dose-dependent manner.

Genetic and plasma markers of venous thromboembolism in patients with high grade glioma.

Purpose: Deep venous thrombosis/pulmonary embolism (DVT/PE) is a frequent complication in the course of cancer, particularly in brain tumors. We investigated genetic and plasma factors possibly associated with risk of DVT/PE in patients with high-grade glioma.

Experimental Design: In a case-control study, we studied polymorphisms of the genes coding for factor II (G20210A), factor V (G1691A), methylenetetrahydrofolate-reductase (C677T), tissue-type plasminogen activator (tPA; insertion/deletion), plasminogen activator inhibitor-1 (PAI-1; 4G/5G), and vascular endothelial growth factor (VEGF; C936T).

Intracavitary VEGF, bFGF, IL-8, IL-12 levels in primary and recurrent malignant glioma.

Intracavitary levels of VEGF, bFGF, IL-8 and IL- 12 were evaluated by ELISA in 45 patients, 7 with recurrent anaplastic astrocytoma (rAA), 12 with glioblastoma (GBM) and 26 with recurrent glioblastoma (rGBM). In 25 patients plasma levels of the molecules were also quantitated. Twenty-three healthy controls were also studied for plasma concentrations of the same molecules.