A total of 242 healthy adults were immunised with a first dose of an investigational inactivated hepatitis A vaccine. Three concentrations (3, 6 and 12 EU ELISA units) of the experimental vaccine ...were used and compared to a licensed reference vaccine. The aim was to determine the antigenic concentration of the study vaccine inducing the highest seroconversion rate and anti-Hepatitis A virus (HAV) antibody response at 2 weeks after the primary immunisation. A booster dose was given at month 6. At 15 days after the primary immunisation the seroconversion rates in subjects vaccinated with the 6 and 12 EU vaccines were 78 and 94%, respectively. At 30 and 180 days after the primary immunisation the percentages of seropositivity were 100% for both groups. The antibody response to the 12 EU study vaccine was similar to that to the reference vaccine. The percentages of seropositivity at 15 and 180 days after the primary immunisation were 94 vs 93%, and 100 vs 93% in the experimental and reference vaccine respectively. Thus, because it induces early and lasting seroconversion, the 12 EU study vaccine seems to be the most effective as a high potency HAV vaccine.
Secondary malignancies are a well-known late complication occurring in patients who undergo bone marrow transplant (BMT) during childhood. A boy with acute lymphoblastic leukemia experienced a BM ...relapse at the age of 14 years and underwent an autologous BMT conditioned with TBI and melphalan. Sixteen years later a malignant mesothelioma of the peritoneum was diagnosed. A surgical approach according to the Sugarbaker technique and hyperthermic peritoneal perfusion with CDDP and Adriamycin were performed. The patient is alive and well after a follow-up of 20 months. To the authors' knowledge this is the first case of mesothelioma as a secondary malignancy after BMT.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
14.
Aurora B kinase and malignant mesothelioma Betta, P.; Bensi, T.; Trincheri, N. F. ...
Journal of clinical oncology,
05/2010, Letnik:
28, Številka:
15_suppl
Journal Article
Abstract only
e22102
Background: There is still no single test that can reliably identify malignant mesothelial cells. Recently soluble MES and OPN have been proposed as novel serum markers for MPM ...but a definitive consensus on their use in routine is still lacking. This study aims at 1. analysing the essential pathological features of a series of consecutive MPMs from a single institution and 2. assessing the tumour tissue expression of OPN and MES and speculating about the potential biological role of these molecules in MPM. Methods: All MPMs diagnosed between 1999 and 2008 were retrieved from the archives of the Pathology Unit of Alessandria Hospital. All the diagnoses had been made on the basis of conventional light microscopy features supplemented by a mucin stain (periodic acid-Schiff with and without diastase treatment) and a panel of immunostains (carcinoembryonic antigen, CD15/LeuM1, BerEP4, calretinin and cytokeratin 5). Immunostaining for OPN (polyclonal antibody) and MES (monoclonal antibody, clone 5B2) was performed using the labelled streptavidin-biotin method, and the staining intensity and extent were assessed. Results: The study group consisted of 50 males and 20 females with a mean age at diagnosis of 78.4 years (range 47–92). Histopathology was epithelial, mixed, and sarcomatous in 52, 12, and 6 patients respectively. OPN positivity (percentage of positive tumour cells >10%) was observed in 67 MPMs (96%) mostly in a granular cytoplasmic pattern and with an intensity ranging from weak (25%) to moderate (31%) and strong (44%). MES positivity (percentage of positive tumour cells >10%) was recorded in 60 MPMs (86%), of which 36% exhibited a weak, 36% a moderate and 28% a strong immunostaining in a membrane pattern. MES was positive in 100% of epithelial MPMs, in 67% of mixed and in 0% of sarcomatous. Positivity was restricted to the epithelial component in mixed MPMs. Conclusions: The high expression of OPN in MPM, irrespective of the histotype, seems to point to a role of this molecule as a marker of malignant transformation of mesothelial cells, while the restriction of positive staining for MES to the epithelial phenotype supports a role of MES as a marker of epithelial differentiation in MPM.
No significant financial relationships to disclose.
Cadherins and their associated cytoplasmic proteins, catenins, are critical to the maintenance of normal tissue integrity and the suppression of cancer invasion. The cadherin profile in malignant ...mesothelioma (MM) is not well defined and the role of the cadherin–catenin system in the pathogenesis of MM remains to be determined. By means of Western blot analysis and immunohistochemistry the expression of E (epithelial)-, N (neural)-, P (placental)-cadherin, and α-, β- and γ-catenins was studied in nine human MM cell lines and five human mesothelial cell lines. Mesothelial cells consistently expressed only N-cadherin and α- and β-catenins. All but one MM cell line were N-cadherin-positive and all of them were also positive for α- and β-catenins. E-cadherin was found in six (66.7%) and γ-catenin in seven (77.8%) MM cell lines. Five of these E-cadherin-positive lines co-expressed N-cadherin and the remaining one was also P-cadherin-positive. Double immunofluorescence staining revealed the plasma membrane co-localisation of both cadherin types in MM cell lines that co-expressed E- and N-cadherin or E- and P-cadherin, respectively. Immunoprecipitation showed complexes of β-catenin with both cadherin types when co-expressed. The results point to upregulation of E-cadherin and γ-catenin in most MM cases and demonstrate that cadherin expression is more heterogeneous and less mutually exclusive in MM compared with the mesothelium, although the biological significance of this finding remains unclear.
Ron (the receptor for Macrophage Stimulating Protein) has never been implicated before in human malignancies or in cell transformation. In this report we show that Ron can acquire oncogenic potential ...by means of two amino acid substitutions-D1232V and M1254T-affecting highly conserved residues in the tyrosine kinase domain. The same mutations in Kit and Ret have been found associated with two human malignancies, mastocytosis and Multiple Endocrine Neoplasia type 2B (MEN2B), respectively. Both mutations caused Ron-mediated transformation of 3T3 fibroblasts and tumour formation in nude mice. Moreover, cells transformed by the oncogenic Ron mutants displayed high metastatic potential. The Ron mutant receptors were constitutively active and the catalytic efficiency of the mutated kinase was higher than that of wild-type Ron. Oncogenic Ron mutants enhanced activation of the Ras/MAPK cascade with respect to wild type Ron, without affecting the JNK/SAPK pathway. Expression of Ron mutants in 3T3 fibroblasts led to different patterns of tyrosine-phos-phorylated proteins. These data show that point mutations altering catalytic properties and possibly substrate specificity of the Ron kinase may force cells toward tumorigenesis and metastasis.
Abstract only
18097
Background: While no previous data has so far shown any difference between the efficacy of serum platelet-derived growth factor (PDGF-AB) and serum epidermal growth factor (EGF) ...in distinguishing MPM from benign pleural diseases, some pilot studies have shown the potentiality of both these markers in the prognosis of MPM patients. This study investigates this capacity by analyzing survival in a series of MPM patients. Methods: Using an ELISA method, EGF (ng/ml) baseline serum was determined in 83 newly diagnosed MPM patients, and in 62 cases PDGF-AB serum levels were also measured. After a median follow-up time of 11.8 months (range 0.4–52.1 months), the log-rank test was used to compare the survival curves, and Cox’s regression analysis was also performed. Results: Median serum values were 0.56 ng/ml (range 0.09–2.05) for EGF and 43.0 ng/ml (range 0.1–145) for PDGF-AB. Patients with EGF levels higher than the median level of 0.56 ng/ml had an average survival time of 9.4 months (95%CI: 5.7–13.2), while the average survival time of patients with below-median EGF levels was 13.2 months (95%CI: 10.6–15.8); a statistically significant difference (p=0.005). For patients with PDGF-AB levels higher than an assumed cut-off of 49.8 ng/ml, (above 75
th
percentile of MPM marker concentration) average survival was 7.9 months (95%CI: 4.5–11.3) as against the 14.9 months (95%CI: 10.3–18.7) in patients with below cut-off marker levels, again statistically significant (p=0.02). Cox’s regression analysis was performed on 42 patients in whom data on age, sex, histology, stage and platelet count were available. EGF and PDGF-AB levels higher than the selected cut-offs were confirmed as independent predictors of poor survival (HR=1.49; 95% CI: 1.04–2.13; p=0.03 and HR=1.96; 95% CI: 1.23–3.13; p=0.005, respectively). Conclusions: Our data suggest that circulating PDGF-AB and EGF levels are promising markers for clinical monitoring of MPM patients.
No significant financial relationships to disclose.
The cytotoxic effects of asbestos are partly mediated by the production of free radicals, including nitric oxide (NO). SV40 has been suggested to synergize with asbestos in the pathogenesis of ...malignant mesothelioma. Crocidolite asbestos fibers induced in human mesothelial and malignant mesothelioma cells a significant increase of NO synthase activity and expression, which was absent in SV40-infected cells. Furthermore, SV40 infection prevented the NF kappa B activation elicited by crocidolite in both mesothelial and mesothelioma cells. These data suggest that SV40, by inhibiting the synthesis of NO, could favor the survival of transformed, potentially neoplastic cells.
Abstract only
10080
Background: MPM is an uncommon but extremely aggressive tumor of the serosal surfaces, which has been closely linked to asbestos exposure. Several in-vitro studies have ...demonstrated that HGF enhances MPM cell proliferation, migration, and invasiveness and the presence of EGF is closely related to the process of cell differentiation and the synthesis of glycosaminoglycans in MPM cells. Few studies have measured the blood levels of these growth factors in tumor patients and assessed their correlation with clinical outcome. This pilot study was designed to investigate the potential value of serum EGF and HGF measurements for the diagnosis and the prediction of survival in MPM patients. Methods: Baseline serum EGF and HGF levels (ng/ml) were determined using an ELISA method in 81 newly diagnosed MPM patients (mean age 67.5±11.0 years) and 48 patients with benign respiratory diseases (BRD; mean age 64.3±13.5 years). Results: HGF and EGF median concentrations in MPM (1.6 ng/ml and 0.5 ng/ml, respectively) were not statistically different from concentrations in BRD (1.2 ng/ml and 0.4 ng/ml). Median follow-up for MPM patients was 27 months, while overall median survival was 11.8 months. At univariate analysis, only high EGF serum levels were associated with an unfavorable survival outcome. Using a cut-off point for EGF of 0.5 ng/ml (corresponding to the median of marker concentration in MPM), the survival rate in patients with higher serum EGF was significantly worse than that in patients with lower levels (median 10.7 vs. 13.0 months, p=0.01). Multivariate analysis, after adjusting for age, sex, histology and platelet count, confirmed the independent predictive value of serum EGF concentration as a negative prognostic factor (p=0.01). Conclusions: High pre-treatment levels of serum EGF are associated with an adverse prognostic impact on survival in MPM patients.
No significant financial relationships to disclose.
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