Publications (49) View all
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Article: Increased migration of a human glioma cell line after in vitro CyberKnife irradiation.
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ABSTRACT: A human glioblastoma multiforme cell line (U87) and its derived-spheroids were irradiated either using a conventional irradiation (CIR) or a CK-like irradiation (IIR) in which the 8 Gy was delivered intermittently over a period of 40 minutes. The ability of glioma cells to migrate into a matrigel matrix was evaluated on days 1-8 from irradiation. Irradiation with CK-driven IIR significantly increased the invasion potential of U87 cells in a matrigel-based assay. In contrast to CIR, IIR was associated with increased levels of TGF-β at four days (Real time PCR), β1-integrin at 4-5 days (real-time PCR and western blot) and no elevation in phosphorylated AKT at days 4 and 5 (western blot). Our data suggests that glioma cell invasion as well as elevations of TGF-β and β1-integrin are associated with IIR and not CIR.Cancer biology & therapy 10/2011; 12(7):629-33. · 2.64 Impact Factor -
Article: In vitro effects of Cyberknife-driven intermittent irradiation on glioblastoma cell lines.
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ABSTRACT: Radiosurgery is used increasingly upon recurrence of high-grade gliomas to deliver a high dose of focused radiation to a defined target. The purpose of our study was to compare intermittent irradiation (IIR) by using a CyberKnife (CK) with continuous irradiation (CIR) by using a conventional linear accelerator (LINAC). A significant decrease in surviving fraction was observed after IIR irradiation compared with after CIR at a dose of 8 Gy. Three hours after irradiation, most of the DNA damage was repaired in U87. Slightly higher basal levels of Ku70/80 mRNA were found in U87 compared with A172, while radiation treatment induced only minor regulation of Ku70/80 and Rad51 transcription in either cell lines. IIR treatment using CK significantly decreased the survival in U87 and A172 compared with CIR. Although the two cell lines differed in DNA repair capability, the role of Ku70/80 and Rad51 in the cell line radiosensitivity seemed marginal.Neurological Sciences 02/2011; 32(4):579-88. · 1.32 Impact Factor -
Article: Intrathecal synthesis of tumor markers is a highly sensitive test in the diagnosis of leptomeningeal metastasis from solid cancers.
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ABSTRACT: Identification of neoplastic cells in cerebrospinal fluid (CSF) by cytological analysis is the key diagnostic feature of leptomeningeal metastasis (LM). Because of the lack of sensitivity of this test, considerable efforts have been made to identify alternative diagnostic markers. Data from the literature suggest that measurement of tumor markers (TM) in CSF may be helpful for improving the diagnosis. We analyzed the concentrations of the TM carcinoembryonic antigen (CEA), CA15.3, CA125 and CA19.9 in both CSF and serum from 18 patients with neoplastic meningitis diagnosed by CSF cytology. We also performed these same measurements in 50 patients affected by other neurological diseases (OND) in order to evaluate putative intrathecal synthesis. In addition, CSF and serum concentrations of the proangiogenic factor VEGF (vascular endothelial growth factor) were evaluated. All LM patients showed intrathecal synthesis for at least one TM. In one patient, a negative CSF cytology after treatment paralleled normalization of tumor marker synthesis. None of the OND patients displayed intrathecal TM synthesis. The VEGF Index (CSF/serum VEGF relative to CSF/serum albumin ratios) was significantly higher in LM patients compared with the control group. However, significant overlap between LM patients and values seen in those with OND was observed. Evaluation of intrathecal TM synthesis is a specific, sensitive, reliable, and reproducible diagnostic tool, and is useful to support diagnosis of carcinomatous meningitis.Clinical Chemistry and Laboratory Medicine 06/2009; 47(7):874-9. · 2.15 Impact Factor -
Article: A phase I-II study of the histone deacetylase inhibitor valproic acid plus chemoimmunotherapy in patients with advanced melanoma.
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ABSTRACT: We explored in a phase I/II clinical trial the combination of valproic acid (VPA), a clinically available histone deacetylase inhibitor, with standard chemoimmunotherapy in patients with advanced melanoma, to evaluate its clinical activity, to correlate the clinical response with the biological activity of VPA and to assess toxicity. Patients were treated initially with VPA alone for 6 weeks. The inhibition of the target in non-tumour peripheral blood cells (taken as a potential surrogate marker) was measured periodically, and valproate dosing adjusted with the attempt to reach a measurable inhibition. After the treatment with valproate alone, dacarbazine plus interferon-alpha was started in combination with valproate. Twenty-nine eligible patients started taking valproate and 18 received chemoimmunotherapy and are assessable for response. We observed one complete response, two partial remissions and three disease stabilisations lasting longer than 24 weeks. With the higher valproate dosages needed to reach a measurable inhibition of the target, we observed an increase of side effects in those patients who received chemoimmunotherapy. The combination of VPA and chemoimmunotherapy did not produce results overtly superior to standard therapy in patients with advanced melanoma and toxicity was not negligible, casting some doubts on the clinical use of VPA in this setting (at least in the administration schedule adopted).British Journal of Cancer 02/2009; 100(1):28-36. · 5.04 Impact Factor -
Article: A new function of microtubule-associated protein tau: involvement in chromosome stability.
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ABSTRACT: Tau is a microtubule-associated protein that promotes assembly and stabilization of cytoskeleton microtubules. It is mostly expressed in neuronal and glial cells but it is also present in non-neural cells such as fibroblasts and lymphocytes. An altered tau produces cytoskeleton pathology resulting in neurodegenerative diseases such as Alzheimer's disease and tauopathies. Tau has been suggested to be a multifunctional protein, due to its localization in different cellular compartments. However its further functions are still unclear. We analyzed the distribution of tau in human skin fibroblasts showing its localization in the nucleus and along mitotic chromosomes. Then, we investigated if an altered tau, such as the P301L mutated protein associated with frontotemporal dementia, could produce nuclear pathology. We found that patients carrying the mutation consistently had several chromosome aberrations in their fibroblasts and lymphocytes: chromosome and chromatid breakages or gaps, aneuploidies, translocations, in addition to chromatin bridges and decondensed chromosomes. Our findings argue for a role of tau in chromosome stability by means of its interaction with both microtubules and chromatin.Cell cycle (Georgetown, Tex.) 04/2008; 7(12):1788-94. · 5.36 Impact Factor
