118,481 research outputs found
Malignant mesothelioma as both a challenge and an opportunity
No full textThe International Mesothelioma Interest Group sponsored its 7th international meeting in Brescia, Italy from June 24-26, 2004. The meeting, entitled 'How advanced technology and new drugs are changing the perspectives of patients with malignant mesothelioma', was organized by Luciano Mutti (Vercelli, Italy) and GF Tassi (Brescia, Italy) and was attended by 350 participants. The general tone of the meeting was that real progress is now coming in the understanding of mesothelioma biology, progress that may soon translate into improved treatment options. The investigators and clinicians agreed on the importance of referring patients with mesothelioma to centers with expertise where patients can receive the best available treatments and can be offered entry into clinical trials of new and promising agents
Editorial: Editor's challenge: Dr. Luciano Mutti - what is the true impact of ICIs on survival in the treatment of thoracic malignancies?
No full textRecurrent chromosome 6 abnormalities in malignant mesothelioma
No full textThe long latency period between asbestos exposure and the onset of malignant mesothelioma (MM) suggests that a multistep tumorigenesis process occurs whilst the capability of asbestos fibres to interfere directly with chromosomes focuses on the critical role of the chromosomal abnormalities in this neoplasm. The aim of our study was to identify any recurrent chromosomal changes in ten primary MM cell cultures derived from pleural effusions of patients with MM from the same geographic area and environmental and/or occupational exposure to asbestos fibres. Cytogenetic analysis was performed in accordance with International System for Human Cytogenetic Nomenclature. Our results confirmed a great number of cytogenetic abnormalities in MM cells. Recurrent loss of the long arms of chromosome 6 (6q-) was the most frequent abnormality detected (four epithelial and two mixed subtypes) while, on the whole, abnormalities of chromosome 6 were found in nine out of ten cases whereas chromosome 6 was normal only in the case with fibromatous subtype. Monosomy 13 and 17 was found in five cases, monosomy 14 in four cases and 22 in three cases. Since deletion of 6q- was detected even in relatively undisturbed karyotype, we hypothesize a multistep carcinogenic process in which deletion of 6q- is an early event in the development and progression of malignant mesothelioma
Immunobiology and immune defence mechanisms of mesothelioma cells
No full textMalignant mesothelioma (MM) is an aggressive tumour whose incidence is expected to rise in future years. Patients with this neoplasm have a poor prognosis. Immunotherapy has been shown to be effective in some neoplasms (e.g. melanoma), significantly improving their prognosis but we do not yet have sufficient data on the capability of MM cells to elicit an immune response. A 'three step' event is required to determine an immune response: adhesion, recognition, and costimulation between the antigen presenting cells and the immunoeffector cells. Lack of one of these three steps leads to a defective immune response. The most important mechanism determining the defective immune response to the tumour cells is supposed to be the deficiency of the molecules involved in this 'three step event', the release of immunodepressant factors by the tumour cells and/or the tumour infiltrating cells and the lack of surface immunogen epitopes. Investigations on MM cells are not univocal, suggesting that, at least in some cases, an effective immune response to this neoplasm can occur. Blocking the release of immunodepressant factors by malignant mesothelioma cells and identification of effective, specific immunogen epitopes seem to be the most promising objectives to achieve
The therapeutic potential of the novel ribonuclease ranpirnase (Onconase®) in the treatment of malignant mesothelioma
No full textRibonucleases are a superfamily of RNA-cleaving enzymes that can be cytotoxic since the cleavage of RNA makes its information indecipherable. Ranpirnase is a novel ribonuclease which preferentially degrades tRNA, thus leading to an inhibition of protein synthesis and, ultimately, to cytostasis and cytotoxicity. Ranpirnase has demonstrated antitumor activity both in vitro and in vivo in several tumor models, including malignant mesothelioma. A large phase II trial showed that ranpirnase has diseasemodifying activity against mesothelioma. A first phase III study demonstrated that rampirnase may be combined with doxorubicin and that such an association is more active than Ranpirnase alone against mesothelioma. At present, another large, phase III trial in combination with doxorubicin has completed enrollment and its results are awaited. In all the above studies, ranpirnase died not demonstrate conventional anticancer activity, stabilizing progressive disease and potentially prolonging patients' survival. Finally, a better understanding of its mechanism of action, coupled with its favorable toxicity profile, especially characterized by the lack of major hematologic toxicities, makes ranpirnase an attractive drug to test in combination with other anticancer agents, in MMe as well as in other tumor types. © Springer-Verlag 2008
BCL-2 family regulation by the 20S proteasome inhibitor bortezomib
No full textBortezomib (Velcade, PS341) was licensed in 2003 as a first-in-class 20S proteasome inhibitor indicated for treatment of multiple myeloma, and is currently being evaluated clinically in a range of solid tumours. The mechanisms underlying its cancer cell toxicity are complex. A growing body of evidence suggests proteasome inhibition-dependent regulation of the BCL-2 family is a critical requirement. In particular, the stabilization of BH3-only proteins BIK, NOXA and BIM, appear to be essential for effecting BAX- and BAK-dependent cell death. These mechanisms are reviewed and the implications for favourable novel drug interactions are highlighted. © 2008 Nature Publishing Group All rights reserved
Biomimetic Modeling of Copper Complexes: A Study of Enantioselective Catalytic Oxidation on D-(+)-Catechin and L-(−)-Epicatechin with Copper Complexes
No full textThe biomimetic catalytic oxidations of the dinuclear and trinuclear copper(II) complexes versus two catechols, namely, D-(+)-catechin and L-(−)-epicatechin to give the corresponding quinones are reported. The unstable quinones were trapped by the nucleophilic reagent, 3-methyl-2-benzothiazolinone hydrazone (MBTH), and have been calculated the molar absorptivities of the different quinones. The catalytic efficiency is moderate, as inferred by kinetic constants, but the complexes exhibit significant enantio-differentiating ability towards the catechols, albeit for the dinuclear complexes, this enantio-differentiating ability is lower. In all cases, the preferred enantiomeric substrate is D-(+)-catechin to respect the other catechol, because of the spatial disposition of this substrate
Negative results of an Italian Group for Mesothelioma (G.I.Me.) pilot study of single-agent imatinib mesylate in malignant pleural mesothelioma
No full textInhibition of Ascorbate Oxidase by 2-methyl-2,4-pentanediol and other polyols
No full textThe organic alcohol 2-methyl-2,4-pentanediol, which is used as cosolvent in the aqueous buffer to induce crystallization of ascorbate oxidase, acts as a competitive inhibitor of ascorbic acid in the oxidase reaction. Glycerol and ethylene glycol show similar, but smaller inhibitory effects. The lower activity exhibited by crystalline ascorbate oxidase with respect to the native enzyme has been shown to depend on the ageing of the proteine solution during crystallization and not by specific effects due to the presence of 2-methyl-2,4-pentanediol
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