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.Plasma levels of VEGF (mean 33.89 ± 6.71pg/ml) and bFGF (mean 11.1 ± 3.24pg/ml) were higher in patients than in controls (mean 16.78 ± 3.7pg/ml for VEGF, mean 0.21 ± 0.09pg/ml for bFGF) (p = 0.04 and p = 0.001, respectively) while plasma IL-12 levels were lower (mean 45.6 ± 1.5pg/ml in patients, mean 79.7 ± 1.3pg/ml in controls) (p = 0.009).Intracavitary VEGF levels were 5–53.307 fold higher (mean 90,900 ± 24,789pg/ml) than in the corresponding plasma. Also IL-8 concentrations were higher in intracavitary fluid (mean 6,349.76 ± 1,460.93pg/ml) than in plasma (mean 43.44 ± 24.82pg/ml). Maximum VEGF levels were found in tumor fluid of recurrent glioblastoma patients (mean 147,678 ± 39,903pg/ml), intermediate levels in glioblastoma patients (mean 20,322 ± 11,892pg/ml) and lower levels in rAA patients (mean 9,111 ± 5,789pg/ml). The data also suggest that higher intracavitary levels of VEGF and IL-8, and lower IL-12 levels, may be correlated with shorter adjunctive survival times, but more data will need to be collected to establish this correlation clearly.     

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. RESULTS: MGMT methylation was detected by methylation-specific PCR in 41 of 86 cases (47.7%; Meth+). Progression-free survival and overall survival were significantly longer in Meth+ than in Meth- patients [10 versus 7 months (P=0.003, log-rank test) and 18 versus 14 months (P=0.0003, log-rank test), respectively]. Mixed-nodular enhancement at magnetic resonance imaging was significantly more frequent in Meth+ and secondary glioblastoma multiforme and ring enhancement in Meth- and primary glioblastoma multiforme (P<0.005). MGMT methylation was more present in secondary glioblastoma multiforme (P=0.006) and associated with loss of heterozygosity on 17p and/or 19q (P=0.005). CONCLUSIONS: These observations suggest that MGMT methylation is part of a genetic signature of glioblastomas that developed from lower-grade gliomas.     

Usefulness of the LigaSure vessel sealing system during superficial lobectomy of the parotid gland

OBJECTIVE: To evaluate the usefulness of the LigaSure Precise instrument in superficial lobectomy of the parotid gland. DESIGN: Prospective study of the surgical procedures in the LigaSure Vessel Sealing System and comparison with a conventionally treated control group. SETTING: Secondary care academic referral center.Patients Thirty-five patients with a parotid gland benign tumor were randomly allocated to 2 superficial lobe parotidectomy groups: 17 using the LigaSure procedure (group A) and 18 using the conventional method (group B). MAIN OUTCOME MEASURES: During the past few years, different methods of achieving hemostasis in parotid gland surgery have been tested as means of decreasing operative time and facial nerve injuries by controlling bleeding. With the whole LigaSure Vessel Sealing System, we experienced the usefulness of the LigaSure Precise instrument in superficial lobectomy of the parotid gland. RESULTS: No statistically significant differences were noted between the 2 groups in mean age, tumor diameter, length of hospital stay, time to return to work, or number of adverse events during or after surgery. Operative time was significantly shorter in group A than in group B (P < .001). Total operative time for conservative partial parotidectomy with traditional excision ranged from 115 to 235 minutes (mean, 155.8 minutes). Using the LigaSure system, the mean operative time was 136.4 minutes. Salivary fistulas were more common in group A (3 of 17 patients), with no cases in group B. CONCLUSIONS: The LigaSure method is comparable with but not superior to the conventional method. The main advantages of the LigaSure system are its "sutureless technique" and operative time savings; however, the cost is considerably higher.     

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. We also measured lp(a), VEGF, tPA and PAI-1 in the peripheral circulation of patients, before and after surgery for glioma. VEGF, tPA and PAI-1 were expressed in glioma specimens. Glioma cells were indeed a major source of tPA and PAI-1; these molecules were significantly more expressed in glioma than in patient's blood cells. Lp(a) was rarely expressed in glioma specimens and not expressed in blood cells. In glioma, VEGF, tPA and PAI-1 were localized mainly in tumor cells; tPA was localized also in the extracellular matrix and PAI-1 in tumor vascular lumen. Glioma cells were indeed able to produce and release VEGF, tPA and PAI-1. After surgery, peripheral levels of VEGF and PAI-1 were increased, while tPA and lp(a) were unchanged. The great amount of VEGF, tPA and PAI-1 produced by glioma could influence peripheral levels of these molecules. The partial resection of the tumor by surgery was not able to decrease plasma levels of these molecules.     

Novel Gastrin-Releasing Peptide Receptor Targeted Near-Infrared Fluorescence Dye for Image-Guided Surgery of Prostate Cancer

Molecular Imaging and Biology - Prostate cancer (PCa), the most widespread male cancer in western countries, is generally eradicated by surgery, especially if localized. However, during surgical...     

Platelet met-enkephalin immunoreactivity and 5-hydroxytryptamine concentrations in migraine patients: effects of 5-hydroxytryptophan, amitriptyline and chlorimipramine treatment

In thirty patients with common migraine the platelet concentrations of met-enkephalin immunoreactivity (ME) (76 ± 9 pg/mg protein) were similar to those in 23 healthy volunteers (77 ± 5), suggesting that there is no alteration in the ME pool in this biochemical compartment in migraine. Chronic treatment (4 weeks) with drugs that interfere with 5-hydroxytryptamine (5-HT) synthesis or uptake induced the expected changes in platelet 5-HT levels, i.e. a rise following administration of the 5-HT precursor 5-hydroxytryptophan (daily dose: 300–500 mg, n = 9) and a decrease after amine uptake inhibition by amitryptyline (30–75 mg, n = 7) and even more by chlorimipramine (30–50 mg, n = 9). Platelet ME concentrations rose by up to ∼90% over the basal values after either 5-hydroxytryptophan (significantly from week 2) or amitriptyline (at week 2) and were unchanged after chlorimipramine, indicating that 5-HT and ME concentrations in platelets can vary independently. The high platelet ME levels following 5-hydroxytryptophan and amitriptyline cannot be explained at present. They might be due either to increased ME synthesis, possibly in the megakaryocyte, or to decreased utilization by platelets or both.